Array ( [0] => {{short description|Most abundant type of granulocytes and the most abundant white blood cell}} [1] => {{For|organisms that grow in neutral pH environments|Neutrophile}} [2] => {{cs1 config|name-list-style=vanc|display-authors=6}} [3] => {{Infobox cell [4] => | Name = Neutrophil [5] => | Latin = [6] => | Image2 = Neutrophils.jpg [7] => | Caption2 = Neutrophils with segmented nuclei surrounded by [[erythrocytes]] and [[platelets]]. Intra-cellular granules are visible in the [[cytoplasm]] ([[Giemsa stain]]ed). [8] => | Width = [9] => | Image = Blausen 0676 Neutrophil (crop).png [10] => | Caption = 3D rendering of a neutrophil [11] => | Precursor = [12] => | System = [[Immune system]] [13] => | Function = [[Phagocytosis]] [14] => }} [15] => [16] => '''Neutrophils''' (also known as '''neutrocytes''', '''heterophils''' or '''polymorphonuclear leukocytes''') are a type of [[white blood cell]]. More specifically, they form the most abundant type of [[granulocyte]]s and make up 40% to 70% of all white blood cells in humans.{{cite book | vauthors = Actor J | title = Elsevier's Integrated Review Immunology and Microbiology | date = 2012 | doi = 10.1016/B978-0-323-07447-6.00002-8 | edition = Second }} They form an essential part of the [[innate immune system]], with their functions varying in different animals.{{cite journal | vauthors = Ermert D, Niemiec MJ, Röhm M, Glenthøj A, Borregaard N, Urban CF | title = Candida albicans escapes from mouse neutrophils | journal = Journal of Leukocyte Biology | volume = 94 | issue = 2 | pages = 223–236 | date = August 2013 | pmid = 23650619 | doi = 10.1189/jlb.0213063 | s2cid = 25619835 }} [17] => [18] => They are formed from [[stem cell]]s in the [[bone marrow]] and [[Cellular differentiation|differentiated]] into [[#Subpopulations|subpopulations]] of neutrophil-killers and neutrophil-cagers. They are short-lived (between 5 and 135 hours, see {{slink||Life span}}) and highly mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils (or [[Band cell|bands]]). They form part of the [[polymorphonuclear cells family]] (PMNs) together with [[basophil]]s and [[eosinophil]]s.{{cite journal | vauthors = Witko-Sarsat V, Rieu P, Descamps-Latscha B, Lesavre P, Halbwachs-Mecarelli L | title = Neutrophils: molecules, functions and pathophysiological aspects | journal = Laboratory Investigation; A Journal of Technical Methods and Pathology | volume = 80 | issue = 5 | pages = 617–653 | date = May 2000 | pmid = 10830774 | doi = 10.1038/labinvest.3780067 | s2cid = 22536645 | doi-access = free }}{{cite book | vauthors = Klebanoff SJ, Clark RA | title = The Neutrophil: Function and Clinical Disorders | publisher = Elsevier/North-Holland Amsterdam | year = 1978 | isbn = 978-0-444-80020-6}}{{cite journal | vauthors = Nathan C | title = Neutrophils and immunity: challenges and opportunities | journal = Nature Reviews. Immunology | volume = 6 | issue = 3 | pages = 173–182 | date = March 2006 | pmid = 16498448 | doi = 10.1038/nri1785 | s2cid = 1590558 }} [19] => [20] => The name ''neutrophil'' derives from staining characteristics on [[hematoxylin]] and [[eosin]] ([[H&E stain|H&E]]) [[histology|histological]] or [[cell biology|cytological]] preparations. Whereas [[basophilic]] white blood cells stain dark blue and [[eosinophilic]] white blood cells stain bright red, neutrophils stain a neutral pink. Normally, neutrophils contain a nucleus divided into 2–5 lobes.{{cite book | vauthors = Welsh CJ |title=Hole's Essentials of Human Anatomy and Physiology |date=2021 |publisher=McGraw Hill |location=New York, USA |isbn=978-1-260-57521-7 |page=336 |edition=14th |url=https://www.mheducation.com/highered/product/hole-s-essentials-human-anatomy-physiology-welsh/M9781260251340.html |access-date=28 February 2023}} [21] => [22] => Neutrophils are a type of [[phagocyte]] and are normally found in the [[blood]]stream. During the beginning ([[acute (medical)|acute]]) phase of [[inflammation]], particularly as a result of [[bacteria]]l [[infection]], environmental exposure,{{cite journal | vauthors = Jacobs L, Nawrot TS, de Geus B, Meeusen R, Degraeuwe B, Bernard A, Sughis M, Nemery B, Panis LI | title = Subclinical responses in healthy cyclists briefly exposed to traffic-related air pollution: an intervention study | journal = Environmental Health | volume = 9 | issue = 64 | pages = 64 | date = October 2010 | pmid = 20973949 | pmc = 2984475 | doi = 10.1186/1476-069X-9-64 | doi-access = free | bibcode = 2010EnvHe...9...64J }} and some cancers,{{cite journal | vauthors = Waugh DJ, Wilson C | title = The interleukin-8 pathway in cancer | journal = Clinical Cancer Research | volume = 14 | issue = 21 | pages = 6735–6741 | date = November 2008 | pmid = 18980965 | doi = 10.1158/1078-0432.CCR-07-4843 | s2cid = 9415085 }} [23] => {{cite journal | vauthors = De Larco JE, Wuertz BR, Furcht LT | title = The potential role of neutrophils in promoting the metastatic phenotype of tumors releasing interleukin-8 | journal = Clinical Cancer Research | volume = 10 | issue = 15 | pages = 4895–4900 | date = August 2004 | pmid = 15297389 | doi = 10.1158/1078-0432.CCR-03-0760 | s2cid = 9782495 }} [24] => neutrophils are one of the first responders of inflammatory cells to migrate toward the site of inflammation. They migrate through the blood vessels and then through [[:wikt:interstitial|interstitial]] space, following chemical signals such as [[interleukin-8]] (IL-8), [[Complement component 5a|C5a]], [[N-Formylmethionine leucyl-phenylalanine|fMLP]], [[leukotriene B4]], and [[hydrogen peroxide]] (H2O2){{cite journal | vauthors = Yoo SK, Starnes TW, Deng Q, Huttenlocher A | title = Lyn is a redox sensor that mediates leukocyte wound attraction in vivo | journal = Nature | volume = 480 | issue = 7375 | pages = 109–112 | date = November 2011 | pmid = 22101434 | pmc = 3228893 | doi = 10.1038/nature10632 | bibcode = 2011Natur.480..109Y }} in a process called [[chemotaxis]]. They are the predominant cells in [[pus]], accounting for its whitish/yellowish appearance.{{cite book | vauthors = Barer MR | title=Medical Microbiology | pages=168–173 | chapter=The natural history of infection | publisher=Elsevier | year=2012 | isbn=978-0-7020-4089-4 | doi=10.1016/b978-0-7020-4089-4.00029-9 }} [25] => [26] => Neutrophils are recruited to the site of injury within minutes following trauma and are the hallmark of acute inflammation;{{cite book | vauthors = Cohen S, Burns RC |date=2002 |title=Pathways of the Pulp |edition=8th |publisher=Mosby |location=St. Louis |page=465}} however, due to some [[pathogens]] being indigestible, they might not be able to resolve certain infections without the assistance of other types of immune cells. [27] => [28] => == Structure == [29] => [[File:NeutrophilerAktion.svg|thumb|Neutrophil granulocyte migrates from the blood vessel to the matrix, secreting proteolytic enzymes to dissolve intercellular connections (to the improvement of its mobility) and envelop bacteria through phagocytosis.]] [30] => [[File:Hypersegmented neutrophil - by Gabriel Caponetti,MD.jpg|thumb|right|Hypersegmented neutrophil]] [31] => [32] => When adhered to a surface, neutrophil granulocytes have an average diameter of 12–15 [[micrometre|micrometers]] (µm) in [[blood film|peripheral blood smears]]. In suspension, human neutrophils have an average diameter of 8.85 µm.{{cite journal | vauthors = Niemiec MJ, De Samber B, Garrevoet J, Vergucht E, Vekemans B, De Rycke R, Björn E, Sandblad L, Wellenreuther G, Falkenberg G, Cloetens P, Vincze L, Urban CF | title = Trace element landscape of resting and activated human neutrophils on the sub-micrometer level | journal = Metallomics | volume = 7 | issue = 6 | pages = 996–1010 | date = June 2015 | pmid = 25832493 | doi = 10.1039/c4mt00346b | doi-access = free }} [33] => [34] => With the [[eosinophil]] and the [[basophil granulocyte|basophil]], they form the class of ''polymorphonuclear cells'', named for the [[cell nucleus|nucleus]]' multilobulated shape (as compared to [[lymphocyte]]s and [[monocyte]]s, the other types of white cells). The nucleus has a characteristic lobed appearance, the separate lobes connected by [[chromatin]]. The nucleolus disappears as the neutrophil matures, which is something that happens in only a few other types of nucleated cells.{{cite book | vauthors = Zucker-Franklin D, Greaves MF, Grossi CE, Marmont AM |date=1988 |chapter=Neutrophils |title=Atlas of Blood Cells: Function and Pathology |volume=1 |edition=2nd |location=Philadelphia |publisher=Lea & Ferbiger |isbn=978-0-8121-1094-4}}{{rp|168}} Up to 17% of female human neutrophil nuclei have a drumstick-shaped appendage which contains the [[X-inactivation|inactivated X chromosome]].{{cite journal | vauthors = Karni RJ, Wangh LJ, Sanchez JA | title = Nonrandom location and orientation of the inactive X chromosome in human neutrophil nuclei | journal = Chromosoma | volume = 110 | issue = 4 | pages = 267–274 | date = August 2001 | pmid = 11534818 | doi = 10.1007/s004120100145 | s2cid = 24750407 }} In the cytoplasm, the [[Golgi apparatus]] is small, [[mitochondria]] and [[ribosome]]s are sparse, and the rough [[endoplasmic reticulum]] is absent.{{rp|170}} The cytoplasm also contains about 200 granules, of which a third are [[Azurophilic granule|azurophilic]].{{rp|170}} [35] => [36] => Neutrophils will show increasing segmentation (many segments of the nucleus) as they mature. A normal neutrophil should have 3–5 segments. Hypersegmentation is not normal but occurs in some disorders, most notably [[Vitamin B-12 deficiency|vitamin B12 deficiency]]. This is noted in a manual review of the blood smear and is positive when most or all of the neutrophils have 5 or more segments. [37] => [38] => [[File:Reference ranges for blood tests - white blood cells.png|thumb|upright=1.8|left|[[Reference ranges for blood tests]] of white blood cells, comparing neutrophil amount (shown in pink) with that of other cells]] [39] => [40] => Neutrophils are the most abundant white blood cells in humans (approximately 1011 are produced daily); they account for approximately 50–70% of all white blood cells (leukocytes). The stated normal range for human blood counts varies between laboratories, but a neutrophil count of 2.5–7.5 × 109/L is a standard normal range. People of [[Africa]]n and [[Middle East]]ern descent may have lower counts, which are still normal.{{cite journal | vauthors = Reich D, Nalls MA, Kao WH, Akylbekova EL, Tandon A, Patterson N, Mullikin J, Hsueh WC, Cheng CY, Coresh J, Boerwinkle E, Li M, Waliszewska A, Neubauer J, Li R, Leak TS, Ekunwe L, Files JC, Hardy CL, Zmuda JM, Taylor HA, Ziv E, Harris TB, Wilson JG | title = Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene | journal = PLOS Genetics | volume = 5 | issue = 1 | pages = e1000360 | date = January 2009 | pmid = 19180233 | pmc = 2628742 | doi = 10.1371/journal.pgen.1000360 | doi-access = free }} A report may divide neutrophils into segmented neutrophils and [[band cell|bands]]. [41] => [42] => When circulating in the bloodstream and inactivated, neutrophils are spherical. Once activated, they change shape and become more amorphous or [[amoeba]]-like and can extend [[pseudopods]] as they hunt for [[antigen]]s.{{cite book | vauthors = Edwards SW |date=1994 |title=Biochemistry and physiology of the neutrophil |publisher=Cambridge University Press |isbn=978-0-521-41698-6 |pages=6}} [43] => [44] => The capacity of neutrophils to engulf bacteria is reduced when simple sugars like glucose, fructose as well as sucrose, honey and orange juice were ingested, while the ingestion of starches had no effect. Fasting, on the other hand, strengthened the neutrophils' phagocytic capacity to engulf bacteria. It was concluded that the function, and not the number, of phagocytes in engulfing bacteria was altered by the ingestion of sugars.{{cite journal | vauthors = Sanchez A, Reeser JL, Lau HS, Yahiku PY, Willard RE, McMillan PJ, Cho SY, Magie AR, Register UD | title = Role of sugars in human neutrophilic phagocytosis | journal = The American Journal of Clinical Nutrition | volume = 26 | issue = 11 | pages = 1180–1184 | date = November 1973 | pmid = 4748178 | doi = 10.1093/ajcn/26.11.1180 | quote = These data suggest that the function and not the number of phagocytes was altered by ingestion of sugars. This implicates glucose and other simple carbohydrates in the control of phagocytosis and shows that the effects last for at least 5 hr. On the other hand, a fast of 36 or 60 hr significantly increased (P < 0.001) the phagocytic index | doi-access = free }} In 2007 researchers at the Whitehead Institute of Biomedical Research found that given a selection of sugars on microbial surfaces, the neutrophils reacted to some types of sugars preferentially. The neutrophils preferentially engulfed and killed beta-1,6-glucan targets compared to beta-1,3-glucan targets.{{cite journal | vauthors = Rubin-Bejerano I, Abeijon C, Magnelli P, Grisafi P, Fink GR | title = Phagocytosis by human neutrophils is stimulated by a unique fungal cell wall component | journal = Cell Host & Microbe | volume = 2 | issue = 1 | pages = 55–67 | date = July 2007 | pmid = 18005717 | pmc = 2083279 | doi = 10.1016/j.chom.2007.06.002 }}{{cite web | vauthors = Kneller A |date=2007 |title=White blood cells are picky about sugar |publisher=Whitehead Institute |url=http://wi.mit.edu/news/archive/2007/white-blood-cells-are-picky-about-sugar |access-date=2013-08-09}} [45] => [46] => ==Development== [47] => ===Life span=== [48] => [[File:Hematopoiesis simple.svg|thumb|upright=1.8|HSC=[[hematopoietic stem cell]], Progenitor=[[progenitor cell]], L-blast=[[lymphoblast]], [[lymphocyte]], Mo-blast=[[monoblast]], [[monocyte]], [[myeloblast]], Pro-M=[[promyelocyte]], [[myelocyte]], Meta-M=[[metamyelocyte]], neutrophil, [[eosinophil]], basophil, Pro-E=proerythroblast, Baso-E=basophilic erythroblast, poly-e=[[polychromatic]] erythroblast, ortho-E=orthochromatic erythroblast, [[erythrocyte]], [[promegakaryocyte]], [[megakaryocyte]], [[platelet]] ]] [49] => [50] => The average lifespan of inactivated human neutrophils in the circulation has been reported by different approaches to be between 5 and 135 hours.{{cite journal |vauthors = Tak T, Tesselaar K, Pillay J, Borghans JA, Koenderman L |title = What's your age again? Determination of human neutrophil half-lives revisited |journal = Journal of Leukocyte Biology |volume = 94 |issue = 4 |pages = 595–601 |date = October 2013 |pmid = 23625199 |doi = 10.1189/jlb.1112571 |s2cid = 40113921 }}{{cite journal |vauthors = Pillay J, den Braber I, Vrisekoop N, Kwast LM, de Boer RJ, Borghans JA, Tesselaar K, Koenderman L |title = In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days |journal = Blood |volume = 116 |issue = 4 |pages = 625–627 |date = July 2010 |pmid = 20410504 |doi = 10.1182/blood-2010-01-259028|s2cid = 909519 |doi-access = free }} [51] => [52] => Upon activation, they marginate (position themselves adjacent to the blood vessel endothelium) and undergo [[selectin]]-dependent capture followed by [[integrin]]-dependent adhesion in most cases, after which they migrate into tissues, where they survive for 1–2 days. Neutrophils have also been demonstrated to be released into the blood from a [[splenic]] reserve following [[myocardial infarction]].{{cite journal | vauthors = Akbar N, Braithwaite AT, Corr EM, Koelwyn GJ, van Solingen C, Cochain C, Saliba AE, Corbin A, Pezzolla D, Møller Jørgensen M, Bæk R, Edgar L, De Villiers C, Gunadasa-Rohling M, Banerjee A, Paget D, Lee C, Hogg E, Costin A, Dhaliwal R, Johnson E, Krausgruber T, Riepsaame J, Melling GE, Shanmuganathan M, Bock C, Carter DR, Channon KM, Riley PR, Udalova IA, Moore KJ, Anthony DC, Choudhury RP | title = Rapid neutrophil mobilization by VCAM-1+ endothelial cell-derived extracellular vesicles | journal = Cardiovascular Research | volume = 119 | issue = 1 | pages = 236–251 | date = March 2023 | pmid = 35134856 | pmc = 10022859 | doi = 10.1093/cvr/cvac012 }} [53] => [54] => Neutrophils are much more numerous than the longer-lived [[monocyte]]/[[macrophage]] phagocytes. A [[pathogen]] (disease-causing microorganism or virus) is likely to first encounter a neutrophil. Some experts hypothesize that the short lifetime of neutrophils is an [[evolution]]ary adaptation. The short lifetime of neutrophils minimizes propagation of those pathogens that [[parasite|parasitize]] phagocytes (e.g. [[Leishmania]]{{cite journal | vauthors = Ritter U, Frischknecht F, van Zandbergen G | title = Are neutrophils important host cells for Leishmania parasites? | journal = Trends in Parasitology | volume = 25 | issue = 11 | pages = 505–510 | date = November 2009 | pmid = 19762280 | doi = 10.1016/j.pt.2009.08.003 }}) because the more time such parasites spend outside a host [[cell (biology)|cell]], the more likely they will be destroyed by some component of the body's defenses. Also, because neutrophil [[antimicrobial]] products can also damage host [[tissue (biology)|tissue]]s, their short life limits damage to the host during [[inflammation]].{{cite book |vauthors = Wheater PR, Stevens A |date=2002 |title=Wheater's basic histopathology: a colour atlas and text |publisher=Churchill Livingstone |location=Edinburgh |isbn=978-0-443-07001-3 }} [55] => [56] => Neutrophils will be removed after [[phagocytosis]] of pathogens by macrophages. [[PECAM-1]] and [[phosphatidylserine]] on the cell surface are involved in this process. [57] => [58] => == Function == [59] => === Chemotaxis === [60] => Neutrophils undergo a process called [[chemotaxis]] via [[amoeboid movement]], which allows them to migrate toward sites of infection or inflammation. Cell surface receptors allow neutrophils to detect chemical gradients of molecules such as [[interleukin-8]] (IL-8), [[interferon gamma]] (IFN-γ), C3a, [[Complement component 5a|C5a]], and [[leukotriene B4]], which these cells use to direct the path of their migration. [61] => [62] => Neutrophils have a variety of specific receptors, including ones for [[Complement system|complement]], cytokines like [[interleukin]]s and IFN-γ, [[chemokine]]s, [[lectin]]s, and other proteins. They also express receptors to detect and adhere to [[endothelium]] and [[Fc receptor]]s for [[opsonin]].{{cite book |vauthors = Serhan CN, Ward PA, Gilroy DW |date=2010 |title=Fundamentals of Inflammation |publisher=Cambridge University Press |isbn=978-0-521-88729-8 |pages=53–54 |url=https://books.google.com/books?id=cJq1RMPKEYkC&q=receptors+neutrophils&pg=PA54}} [63] => [64] => In leukocytes responding to a [[chemoattractant]], the [[cell polarity#Migratory cells|cellular polarity]] is regulated by activities of small [[Rho family of GTPases|Rho]] [[guanosine triphosphatase]]s ([[Rho family of GTPases|Rho GTPases]]) and the [[phosphoinositide 3-kinase]]s ([[PI3K]]s). In neutrophils, lipid products of PI3Ks regulate activation of Rac1, hematopoietic Rac2, and RhoG GTPases of the Rho family and are required for [[cell motility]]. [[Rac (GTPase)|Rac-GTPases]] regulate cytoskeletal dynamics and facilitate neutrophils adhesion, migration, and spreading.{{cite journal |vauthors = Pantarelli C, Welch HC | title = Rac-GTPases and Rac-GEFs in neutrophil adhesion, migration and recruitment |journal = European Journal of Clinical Investigation |volume = 48 |issue = Suppl 2 |pages = e12939 |date = November 2018 |pmid = 29682742 |pmc = 6321979 |doi = 10.1111/eci.12939 }} They accumulate asymmetrically to the [[plasma membrane]] at the leading edge of polarized cells. Spatially regulating Rho GTPases and organizing the leading edge of the cell, PI3Ks and their lipid products could play pivotal roles in establishing leukocyte polarity, as compass molecules that tell the cell where to crawl. [65] => [66] => It has been shown in mice that in certain conditions neutrophils have a specific type of migration behaviour referred to as [[neutrophil swarming]] during which they migrate in a highly coordinated manner and accumulate and cluster to sites of inflammation.{{cite journal |vauthors = Lämmermann T, Afonso PV, Angermann BR, Wang JM, Kastenmüller W, Parent CA, Germain RN |title = Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo |journal = Nature |volume = 498 |issue = 7454 | pages = 371–375 |date = June 2013 |pmid = 23708969 |pmc = 3879961 |doi = 10.1038/nature12175 |bibcode = 2013Natur.498..371L}} [67] => [68] => ===Anti-microbial function=== [69] => Being highly [[motility|motile]], neutrophils quickly congregate at a focus of [[infection]], attracted by [[cytokine]]s expressed by activated [[endothelium]], [[mast cell]]s, and [[macrophage]]s. Neutrophils express{{cite journal | vauthors = Ear T, McDonald PP | title = Cytokine generation, promoter activation, and oxidant-independent NF-kappaB activation in a transfectable human neutrophilic cellular model | journal = BMC Immunology | volume = 9 | pages = 14 | date = April 2008 | pmid = 18405381 | pmc = 2322942 | doi = 10.1186/1471-2172-9-14 | doi-access = free }} and release cytokines, which in turn amplify inflammatory reactions by several other cell types. [70] => [71] => In addition to recruiting and activating other cells of the immune system, neutrophils play a key role in the front-line defense against invading pathogens, and contain a broad range of proteins.Ambatipudi KS, Old JM, Guilhaus M, Raftery M, Hinds L, Deane EM (2006). Proteomic analysis of the neutrophil proteins of the Tammar wallaby (''Macropus eugenii''). Comparative Biochemistry and Physiology. Part D: Genomic and Proteomics. 1(3), 283-291. DOI: 10.1016/j.cbd.2006.05.002 Neutrophils have three methods for directly attacking micro-organisms: [[phagocytosis]] (ingestion), [[degranulation]] (release of soluble anti-microbials), and generation of [[neutrophil extracellular traps]] (NETs).{{cite journal | vauthors = Hickey MJ, Kubes P | title = Intravascular immunity: the host-pathogen encounter in blood vessels | journal = Nature Reviews. Immunology | volume = 9 | issue = 5 | pages = 364–375 | date = May 2009 | pmid = 19390567 | doi = 10.1038/nri2532 | s2cid = 8068543 }} [72] => [73] => ===Phagocytosis=== [74] => [[File:Neutrophil with anthrax copy.jpg|right|thumb|[[Scanning electron microscope|Scanning electron micrograph]] of a neutrophil (yellow) phagocytosing [[Bacillus anthracis|anthrax bacilli]] (orange). Scale bar is 5 μm.|alt= Long rod-shaped bacteria, one of which has been partially engulfed by a larger blob-shaped white blood cell. The shape of the cell is distorted by undigested bacterium inside it.]] [75] => [[File:Нейтрофил крови человека фагоцитирует бактерию.webm|right|thumb|Bacterial phagocytosis by neutrophil in human blood, invitro. The video is accelerated by a factor of 8.]] [76] => [77] => Neutrophils are [[phagocyte]]s, capable of ingesting microorganisms or particles. For targets to be recognized, they must be coated in [[opsonin]]s{{snd}}a process known as [[antibody opsonization]]. They can internalize and kill many [[microbe]]s, each phagocytic event resulting in the formation of a [[phagosome]] into which [[reactive oxygen species]] and hydrolytic enzymes are secreted. The consumption of oxygen during the generation of reactive oxygen species has been termed the "[[respiratory burst]]", although unrelated to respiration or energy production. [78] => [79] => The respiratory burst involves the activation of the [[enzyme]] [[NADPH oxidase]], which produces large quantities of [[superoxide]], a reactive oxygen species. Superoxide decays spontaneously or is broken down via enzymes known as [[superoxide dismutase]]s (Cu/ZnSOD and MnSOD), to hydrogen peroxide, which is then converted to [[hypochlorous acid]] (HClO), by the green heme enzyme [[myeloperoxidase]]. It is thought that the bactericidal properties of HClO are enough to kill bacteria phagocytosed by the neutrophil, but this may instead be a step necessary for the activation of proteases.{{cite journal | vauthors = Segal AW | title = How neutrophils kill microbes | journal = Annual Review of Immunology | volume = 23 | issue = 5 | pages = 197–223 | year = 2005 | pmid = 15771570 | pmc = 2092448 | doi = 10.1146/annurev.immunol.23.021704.115653 }} [80] => [81] => Though neutrophils can kill many microbes, the interaction of neutrophils with microbes and molecules produced by microbes often alters neutrophil turnover. The ability of microbes to alter the fate of neutrophils is highly varied, can be microbe-specific, and ranges from prolonging the neutrophil lifespan to causing rapid neutrophil [[lysis]] after phagocytosis. ''[[Chlamydia pneumoniae]]'' and ''[[Neisseria gonorrhoeae]]'' have been reported to delay neutrophil [[apoptosis]].{{cite journal | vauthors = Simons MP, Nauseef WM, Griffith TS, Apicella MA | title = Neisseria gonorrhoeae delays the onset of apoptosis in polymorphonuclear leukocytes | journal = Cellular Microbiology | volume = 8 | issue = 11 | pages = 1780–1790 | date = November 2006 | pmid = 16803582 | doi = 10.1111/j.1462-5822.2006.00748.x | s2cid = 25253422 }} [82] => {{cite journal | vauthors = Chen A, Seifert HS | title = Neisseria gonorrhoeae-mediated inhibition of apoptotic signalling in polymorphonuclear leukocytes | journal = Infection and Immunity | volume = 79 | issue = 11 | pages = 4447–4458 | date = November 2011 | pmid = 21844239 | pmc = 3257915 | doi = 10.1128/IAI.01267-10 }} [83] => {{cite journal | vauthors = van Zandbergen G, Gieffers J, Kothe H, Rupp J, Bollinger A, Aga E, Klinger M, Brade H, Dalhoff K, Maass M, Solbach W, Laskay T | title = Chlamydia pneumoniae multiply in neutrophil granulocytes and delay their spontaneous apoptosis | journal = Journal of Immunology | volume = 172 | issue = 3 | pages = 1768–1776 | date = February 2004 | pmid = 14734760 | doi = 10.4049/jimmunol.172.3.1768 | s2cid = 27422510 | doi-access = free }} [84] => Thus, some bacteria{{snd}}and those that are predominantly intracellular pathogens{{snd}}can extend the neutrophil lifespan by disrupting the normal process of spontaneous apoptosis and/or PICD (phagocytosis-induced cell death). On the other end of the spectrum, some pathogens such as ''[[Streptococcus pyogenes]]'' are capable of altering neutrophil fate after phagocytosis by promoting rapid cell lysis and/or accelerating apoptosis to the point of secondary necrosis.{{cite journal | vauthors = Kobayashi SD, Braughton KR, Whitney AR, Voyich JM, Schwan TG, Musser JM, DeLeo FR | title = Bacterial pathogens modulate an apoptosis differentiation program in human neutrophils | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 19 | pages = 10948–10953 | date = September 2003 | pmid = 12960399 | pmc = 196908 | doi = 10.1073/pnas.1833375100 | doi-access = free }}{{cite journal | vauthors = Kobayashi SD, Malachowa N, DeLeo FR | title = Influence of Microbes on Neutrophil Life and Death | journal = Frontiers in Cellular and Infection Microbiology | volume = 7 | issue = 159 | pages = 159 | year = 2017 | pmid = 28507953 | pmc = 5410578 | doi = 10.3389/fcimb.2017.00159 | doi-access = free }} [[File:CC-BY icon.svg|50px]] Material was copied from this source, which is available under a [https://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International License]. [85] => [86] => ===Degranulation=== [87] => Neutrophils also release an assortment of proteins in three types of granules by a process called [[degranulation]]. The contents of these granules have antimicrobial properties, and help combat infection. [[Glitter cell]]s are [[Granulocyte|polymorphonuclear leukocyte]] neutrophils with granules.{{cite journal | vauthors = Berman LB, Feys JO, Schreiner GE | title = Observations on the glitter-cell phenomenon | journal = The New England Journal of Medicine | volume = 255 | issue = 21 | pages = 989–991 | date = November 1956 | pmid = 13378597 | doi = 10.1056/NEJM195611222552104 }} [88] => [89] => {| class="wikitable" [90] => | '''Granule type''' || '''Protein''' [91] => |- [92] => | [[Azurophil]]ic granules (or "primary granules") || [[Myeloperoxidase]], [[bactericidal/permeability-increasing protein]] (BPI), [[defensin]]s, and the [[serine protease]]s [[neutrophil elastase]], [[ Proteinase 3]] and [[cathepsin G]] [93] => |- [94] => | [[Specific granule]]s (or "secondary granules") || [[Alkaline phosphatase]], [[lysozyme]], [[NADPH oxidase]], [[collagenase]], [[lactoferrin]], [[histaminase]],{{cite journal | vauthors = Ringel EW, Soter NA, Austen KF | title = Localization of histaminase to the specific granule of the human neutrophil | journal = Immunology | volume = 52 | issue = 4 | pages = 649–658 | date = August 1984 | pmid = 6430792 | pmc = 1454675 }} and [[cathelicidin]] [95] => |- [96] => | Tertiary granules || [[Cathepsin]], [[gelatinase]], and [[collagenase]] [97] => |} [98] => [99] => ===Neutrophil extracellular traps=== [100] => In 2004, Brinkmann and colleagues described a striking observation that activation of neutrophils causes the release of web-like structures of DNA; this represents a third mechanism for killing bacteria.{{cite journal | vauthors = Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A | title = Neutrophil extracellular traps kill bacteria | journal = Science | volume = 303 | issue = 5663 | pages = 1532–1535 | date = March 2004 | pmid = 15001782 | doi = 10.1126/science.1092385 | s2cid = 21628300 | bibcode = 2004Sci...303.1532B }} These [[neutrophil extracellular traps]] (NETs) comprise a web of fibers composed of [[chromatin]] and [[serine protease]]s{{cite journal | vauthors = Urban CF, Ermert D, Schmid M, Abu-Abed U, Goosmann C, Nacken W, Brinkmann V, Jungblut PR, Zychlinsky A | title = Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans | journal = PLoS Pathogens | volume = 5 | issue = 10 | pages = e1000639 | date = October 2009 | pmid = 19876394 | pmc = 2763347 | doi = 10.1371/journal.ppat.1000639 | doi-access = free }} that trap and kill extracellular microbes. It is suggested that NETs provide a high local concentration of antimicrobial components and bind, disarm, and kill microbes independent of phagocytic uptake. In addition to their possible antimicrobial properties, NETs may serve as a physical barrier that prevents further spread of pathogens. Trapping of bacteria may be a particularly important role for NETs in [[sepsis]], where NETs are formed within blood vessels.{{cite journal | vauthors = Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, Patel KD, Chakrabarti S, McAvoy E, Sinclair GD, Keys EM, Allen-Vercoe E, Devinney R, Doig CJ, Green FH, Kubes P | title = Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood | journal = Nature Medicine | volume = 13 | issue = 4 | pages = 463–469 | date = April 2007 | pmid = 17384648 | doi = 10.1038/nm1565 | s2cid = 22372863 }} Finally, NET formation has been demonstrated to augment macrophage bactericidal activity during infection.{{cite journal | vauthors = Monteith AJ, Miller JM, Maxwell CN, Chazin WJ, Skaar EP | title = Neutrophil extracellular traps enhance macrophage killing of bacterial pathogens | journal = Science Advances | volume = 7 | issue = 37 | pages = eabj2101 | date = September 2021 | pmid = 34516771 | pmc = 8442908 | doi = 10.1126/sciadv.abj2101 | bibcode = 2021SciA....7.2101M }}{{cite journal | vauthors = Monteith AJ, Miller JM, Beavers WN, Maloney KN, Seifert EL, Hajnoczky G, Skaar EP | title = Mitochondrial Calcium Uniporter Affects Neutrophil Bactericidal Activity during Staphylococcus aureus Infection | journal = Infection and Immunity | volume = 90 | issue = 2 | pages = e0055121 | date = February 2022 | pmid = 34871043 | pmc = 8853686 | doi = 10.1128/IAI.00551-21 }} Recently, NETs have been shown to play a role in inflammatory diseases, as NETs could be detected in [[preeclampsia]], a pregnancy-related inflammatory disorder in which neutrophils are known to be activated.{{cite journal | vauthors = Gupta AK, Hasler P, Holzgreve W, Hahn S | title = Neutrophil NETs: a novel contributor to preeclampsia-associated placental hypoxia? | journal = Seminars in Immunopathology | volume = 29 | issue = 2 | pages = 163–167 | date = June 2007 | pmid = 17621701 | doi = 10.1007/s00281-007-0073-4 | s2cid = 12887059 }} Neutrophil NET formation may also impact [[cardiovascular disease]], as NETs may influence [[thrombus]] formation in [[coronary arteries]].{{cite journal | vauthors = Hoyer FF, Nahrendorf M | title = Neutrophil contributions to ischaemic heart disease | journal = European Heart Journal | volume = 38 | issue = 7 | pages = 465–472 | date = February 2017 | pmid = 28363210 | doi = 10.1093/eurheartj/ehx017 | doi-access = free }}{{cite journal | vauthors = Mangold A, Alias S, Scherz T, Hofbauer M, Jakowitsch J, Panzenböck A, Simon D, Laimer D, Bangert C, Kammerlander A, Mascherbauer J, Winter MP, Distelmaier K, Adlbrecht C, Preissner KT, Lang IM | title = Coronary neutrophil extracellular trap burden and deoxyribonuclease activity in ST-elevation acute coronary syndrome are predictors of ST-segment resolution and infarct size | journal = Circulation Research | volume = 116 | issue = 7 | pages = 1182–1192 | date = March 2015 | pmid = 25547404 | doi = 10.1161/CIRCRESAHA.116.304944 | s2cid = 2532741 | doi-access = free }} [101] => NETs are now known to exhibit pro-[[Thrombosis|thrombotic]] effects both ''in vitro''{{cite journal | vauthors = Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD, Wrobleski SK, Wakefield TW, Hartwig JH, Wagner DD | title = Extracellular DNA traps promote thrombosis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 36 | pages = 15880–15885 | date = September 2010 | pmid = 20798043 | pmc = 2936604 | doi = 10.1073/pnas.1005743107 | doi-access = free | bibcode = 2010PNAS..10715880F }} and ''in vivo''.{{cite journal | vauthors = Brill A, Fuchs TA, Savchenko AS, Thomas GM, Martinod K, De Meyer SF, Bhandari AA, Wagner DD | title = Neutrophil extracellular traps promote deep vein thrombosis in mice | journal = Journal of Thrombosis and Haemostasis | volume = 10 | issue = 1 | pages = 136–144 | date = January 2012 | pmid = 22044575 | pmc = 3319651 | doi = 10.1111/j.1538-7836.2011.04544.x }}{{cite journal | vauthors = Borissoff JI, ten Cate H | title = From neutrophil extracellular traps release to thrombosis: an overshooting host-defense mechanism? | journal = Journal of Thrombosis and Haemostasis | volume = 9 | issue = 9 | pages = 1791–1794 | date = September 2011 | pmid = 21718435 | doi = 10.1111/j.1538-7836.2011.04425.x | s2cid = 5368241 | doi-access = free }} More recently, in 2020 NETs were implicated in the formation of blood clots in cases of severe [[COVID-19]].{{cite journal | vauthors = Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, Blair C, Weber A, Barnes BJ, Egeblad M, Woods RJ, Kanthi Y, Knight JS | title = Neutrophil extracellular traps in COVID-19 | journal = JCI Insight | volume = 5 | issue = 11 | page = e138999 | date = June 2020 | pmid = 32329756 | pmc = 7308057 | doi = 10.1172/jci.insight.138999 | s2cid = 216109364 }} [102] => [103] => === Tumor Associated Neutrophils === [104] => [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137580/ TANs] can exhibit an elevated extracellular acidification rate when there is an increase in glycolysis levels.{{cite journal | vauthors = Ancey PB, Contat C, Boivin G, Sabatino S, Pascual J, Zangger N, Perentes JY, Peters S, Abel ED, Kirsch DG, Rathmell JC, Vozenin MC, Meylan E | title = GLUT1 Expression in Tumor-Associated Neutrophils Promotes Lung Cancer Growth and Resistance to Radiotherapy | journal = Cancer Research | volume = 81 | issue = 9 | pages = 2345–2357 | date = May 2021 | pmid = 33753374 | pmc = 8137580 | doi = 10.1158/0008-5472.CAN-20-2870 }} When there is a metabolic shift in TANS this can lead to tumor progression in certain areas of the body, such as the lungs. TANs support the growth and progression of tumors unlike normal neutrophils which would inhibit tumor progression through the phagocytosis of tumor cells. Utilizing a mouse model, they identified that both Glut1 and glucose metabolism increased in TANs found within a mouse who possessed lung adenocarcinoma. [105] => [106] => ==Clinical significance== [107] => [[File:Neutrophils -1.jpg|thumb|Micrograph showing several neutrophils during an acute inflammation]] [108] => Low neutrophil counts are termed ''[[neutropenia]]''. This can be [[congenital disorder|congenital]] (developed at or before birth) or it can develop later, as in the case of [[aplastic anemia]] or some kinds of [[leukemia]]. It can also be a [[adverse effect (medicine)|side-effect]] of [[medication]], most prominently [[chemotherapy]]. Neutropenia makes an individual highly susceptible to infections. It can also be the result of colonization by intracellular neutrophilic parasites. [109] => [110] => In [[alpha 1-antitrypsin deficiency]], the important [[neutrophil elastase]] is not adequately inhibited by [[alpha 1-antitrypsin]], leading to excessive tissue damage in the presence of inflammation – the most prominent one being [[emphysema]]. Negative effects of elastase have also been shown in cases when the neutrophils are excessively activated (in otherwise healthy individuals) and release the enzyme in extracellular space. Unregulated activity of neutrophil elastase can lead to disruption of pulmonary barrier showing symptoms corresponding with [[Acute respiratory distress syndrome|acute lung injury]].{{cite journal | vauthors = Kawabata K, Hagio T, Matsuoka S | title = The role of neutrophil elastase in acute lung injury | journal = European Journal of Pharmacology | volume = 451 | issue = 1 | pages = 1–10 | date = September 2002 | pmid = 12223222 | doi = 10.1016/S0014-2999(02)02182-9 }} The enzyme also influences activity of macrophages by cleaving their [[toll-like receptor]]s (TLRs) and downregulating [[cytokine]] expression by inhibiting nuclear translocation of [[NF-κB]].{{cite journal | vauthors = Domon H, Nagai K, Maekawa T, Oda M, Yonezawa D, Takeda W, Hiyoshi T, Tamura H, Yamaguchi M, Kawabata S, Terao Y | title = Neutrophil Elastase Subverts the Immune Response by Cleaving Toll-Like Receptors and Cytokines in Pneumococcal Pneumonia | journal = Frontiers in Immunology | volume = 9 | pages = 732 | date = 2018 | pmid = 29922273 | pmc = 5996908 | doi = 10.3389/fimmu.2018.00732 | doi-access = free }} [111] => [112] => In [[Familial Mediterranean fever]] (FMF), a mutation in the ''pyrin'' (or ''[[marenostrin]]'') gene, which is expressed mainly in neutrophil granulocytes, leads to a constitutively active [[acute-phase protein|acute-phase response]] and causes attacks of [[fever]], [[arthralgia]], [[peritonitis]], and – eventually – [[amyloidosis]].{{cite journal | vauthors = Ozen S | title = Familial mediterranean fever: revisiting an ancient disease | journal = European Journal of Pediatrics | volume = 162 | issue = 7–8 | pages = 449–454 | date = July 2003 | pmid = 12751000 | doi = 10.1007/s00431-003-1223-x | s2cid = 3464945 }} [113] => [114] => Hyperglycemia can lead to neutrophil dysfunction. Dysfunction in the neutrophil biochemical pathway [[myeloperoxidase]] as well as reduced degranulation are associated with hyperglycemia.{{cite journal | vauthors = Xiu F, Stanojcic M, Diao L, Jeschke MG | title = Stress hyperglycemia, insulin treatment, and innate immune cells | journal = International Journal of Endocrinology | volume = 2014 | pages = 486403 | date = 8 May 2014 | pmid = 24899891 | pmc = 4034653 | doi = 10.1155/2014/486403 | doi-access = free }} [115] => [116] => The [[Absolute neutrophil count]] (ANC) is also used in diagnosis and prognosis. ANC is the gold standard for determining severity of neutropenia, and thus neutropenic fever. Any ANC < 1500 cells / mm3 is considered neutropenia, but <500 cells / mm3 is considered severe.{{cite journal | vauthors = Al-Gwaiz LA, Babay HH | title = The diagnostic value of absolute neutrophil count, band count and morphologic changes of neutrophils in predicting bacterial infections | journal = Medical Principles and Practice | volume = 16 | issue = 5 | pages = 344–347 | date = 2007 | pmid = 17709921 | doi = 10.1159/000104806 | s2cid = 5499290 | doi-access = free }} There is also new research tying ANC to [[myocardial infarction]] as an aid in early diagnosis.{{cite journal | vauthors = Khan HA, Alhomida AS, Sobki SH, Moghairi AA, Koronki HE | title = Blood cell counts and their correlation with creatine kinase and C-reactive protein in patients with acute myocardial infarction | journal = International Journal of Clinical and Experimental Medicine | volume = 5 | issue = 1 | pages = 50–55 | date = 2012 | pmid = 22328948 | pmc = 3272686 }}{{cite journal | vauthors = Basili S, Di Francoi M, Rosa A, Ferroni P, Diurni V, Scarpellini MG, Bertazzoni G | title = Absolute neutrophil counts and fibrinogen levels as an aid in the early diagnosis of acute myocardial infarction | journal = Acta Cardiologica | volume = 59 | issue = 2 | pages = 135–140 | date = April 2004 | pmid = 15139653 | doi = 10.2143/ac.59.2.2005167 | s2cid = 37382677 }} Neutrophils promote ventricular tachycardia in acute myocardial infarction.{{cite journal | vauthors = Grune J, Lewis AJ, Yamazoe M, Hulsmans M, Rohde D, Xiao L, Zhang S, Ott C, Calcagno DM, Zhou Y, Timm K, Shanmuganathan M, Pulous FE, Schloss MJ, Foy BH, Capen D, Vinegoni C, Wojtkiewicz GR, Iwamoto Y, Grune T, Brown D, Higgins J, Ferreira VM, Herring N, Channon KM, Neubauer S, Sosnovik DE, Milan DJ, Swirski FK, King KR, Aguirre AD, Ellinor PT, Nahrendorf M | title = Neutrophils incite and macrophages avert electrical storm after myocardial infarction | journal = Nature Cardiovascular Research | volume = 1 | issue = 7 | pages = 649–664 | date = July 2022 | pmid = 36034743 | pmc = 9410341 | doi = 10.1038/s44161-022-00094-w }} [117] => [118] => In [[autopsy]], the presence of neutrophils in the heart or brain is one of the first signs of infarction, and is useful in the timing and [[myocardial infarction diagnosis|diagnosis of myocardial infarction]] and [[stroke]]. [119] => [120] => File:Histopathology of neutrophil infiltration in myocardial infarction.jpg|Neutrophils are seen in a [[myocardial infarction]] at approximately 12–24 hours,{{cite journal | vauthors = Michaud K, Basso C, d'Amati G, Giordano C, Kholová I, Preston SD, Rizzo S, Sabatasso S, Sheppard MN, Vink A, van der Wal AC | title = Diagnosis of myocardial infarction at autopsy: AECVP reappraisal in the light of the current clinical classification | journal = Virchows Archiv | volume = 476 | issue = 2 | pages = 179–194 | date = February 2020 | pmid = 31522288 | pmc = 7028821 | doi = 10.1007/s00428-019-02662-1 | doi-access = free }}
"This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/ {{Webarchive|url=https://web.archive.org/web/20151121114042/http://creativecommons.org/licenses/by/4.0/ |date=2015-11-21 }})" as seen in this [[micrograph]]. [121] => File:Histopathology of thalamus infarction at approximately 24 hours, high magnification, annotated.jpg|In [[stroke]], they are beginning to infiltrate the infarcted brain after 6 to 8 hours.{{cite journal | vauthors = Jickling GC, Liu D, Ander BP, Stamova B, Zhan X, Sharp FR | title = Targeting neutrophils in ischemic stroke: translational insights from experimental studies | journal = Journal of Cerebral Blood Flow and Metabolism | volume = 35 | issue = 6 | pages = 888–901 | date = June 2015 | pmid = 25806703 | pmc = 4640255 | doi = 10.1038/jcbfm.2015.45 }} [122] => [123] => [124] => == Pathogen evasion and resistance == [125] => {{See also|Phagocyte#Pathogen evasion and resistance}} [126] => Just like phagocytes, pathogens may evade or infect neutrophils.{{cite journal | vauthors = Kobayashi SD, Malachowa N, DeLeo FR | title = Neutrophils and Bacterial Immune Evasion | journal = Journal of Innate Immunity | volume = 10 | issue = 5-6 | pages = 432–441 | date = 2018 | pmid = 29642066 | pmc = 6784029 | doi = 10.1159/000487756 }} Some bacterial pathogens evolved various mechanisms such as virulence molecules to avoid being killed by neutrophils. These molecules collectively may alter or disrupt neutrophil recruitment, apoptosis or bactericidal activity. [127] => [128] => Neutrophils can also serve as host cell for various parasites that infects them avoding phagocytosis, including: [129] => [130] => * [[Leishmania major]] – uses neutrophils as vehicle to parasitize phagocytes{{cite journal | vauthors = Ritter U, Frischknecht F, van Zandbergen G | title = Are neutrophils important host cells for Leishmania parasites? | journal = Trends in Parasitology | volume = 25 | issue = 11 | pages = 505–510 | date = November 2009 | pmid = 19762280 | doi = 10.1016/j.pt.2009.08.003 }} [131] => * [[Mycobacterium tuberculosis|M. tuberculosis]]{{cite journal | vauthors = Parker HA, Forrester L, Kaldor CD, Dickerhof N, Hampton MB | title = Antimicrobial Activity of Neutrophils Against Mycobacteria | journal = Frontiers in Immunology | volume = 12 | pages = 782495 | date = 2021-12-23 | pmid = 35003097 | pmc = 8732375 | doi = 10.3389/fimmu.2021.782495 | doi-access = free }} [132] => * [[M. leprae]] [133] => * [[Yersinia pestis]] [134] => * [[Chlamydia pneumoniae]] [135] => [136] => ==Neutrophil antigens== [137] => [138] => There are five (HNA 1–5) sets of neutrophil antigens recognized. The three HNA-1 antigens (a-c) are located on the low affinity Fc-γ receptor IIIb (FCGR3B :[[CD16b]]) The single known HNA-2a antigen is located on [[CD177]]. The HNA-3 antigen system has two antigens (3a and 3b) which are located on the seventh exon of the CLT2 gene ([[SLC44A2]]). The HNA-4 and HNA-5 antigen systems each have two known antigens (a and b) and are located in the β2 [[integrin]]. HNA-4 is located on the αM chain ([[CD11b]]) and HNA-5 is located on the αL integrin unit ([[CD11a]]).{{cite journal | vauthors = Chu HT, Lin H, Tsao TT, Chang CF, Hsiao WW, Yeh TJ, Chang CM, Liu YW, Wang TY, Yang KC, Chen TJ, Chen JC, Chen KC, Kao CY | title = Genotyping of human neutrophil antigens (HNA) from whole genome sequencing data | journal = BMC Medical Genomics | volume = 6 | issue = 1 | pages = 31 | date = September 2013 | pmid = 24028078 | pmc = 3849977 | doi = 10.1186/1755-8794-6-31 | doi-access = free }} {{CC-notice|cc=by2}} [139] => [140] => ==Subpopulations== [141] => [[File:Neutrophil subpopulation.svg|thumb|Activity of neutrophil-killer and neutrophil-cager in NBT test]] [142] => [143] => Two functionally unequal subpopulations of neutrophils were identified on the basis of different levels of their reactive oxygen metabolite generation, membrane permeability, activity of enzyme system, and ability to be inactivated. The cells of one subpopulation with high membrane permeability (neutrophil-killers) intensively generate reactive oxygen metabolites and are inactivated in consequence of interaction with the substrate, whereas cells of another subpopulation (neutrophil-cagers) produce reactive oxygen species less intensively, don't adhere to substrate and preserve their activity.{{cite thesis |type=PhD | vauthors = Ignatov DY |date=2012 |title=Functional heterogeneity of human neutrophils and their role in peripheral blood leukocyte quantity regulation |publisher=Donetsk National Medical University|doi=10.13140/RG.2.2.35542.34884}}{{cite journal | vauthors = Gerasimov IG, Ignatov DI | title = [Functional heterogenicity of human blood neutrophils: generation of oxygen active species] | journal = Tsitologiia | volume = 43 | issue = 5 | pages = 432–436 | year = 2001 | pmid = 11517658 | url = https://www.researchgate.net/publication/11827349 }}{{cite journal | vauthors = Gerasimov IG, Ignatov DI | title = [Neutrophil activation in vitro] | journal = Tsitologiia | volume = 46 | issue = 2 | pages = 155–158 | year = 2004 | pmid = 15174354 | url = https://www.researchgate.net/publication/8533160 }}{{cite journal | vauthors = Gerasimov IG, Ignatov DI, Kotel'nitskiĭ MA | title = [Nitroblue tetrazolium reduction by human blood neutrophils. I. The influence of pH] | journal = Tsitologiia | volume = 47 | issue = 6 | pages = 549–553 | year = 2005 | pmid = 16708848 | url = https://www.researchgate.net/publication/7072581 }}{{cite journal | vauthors = Gerasimov IG, Ignatov DI | title = [Nitroblue tetrazolium reduction by human blood neutrophils. II. The influence of sodium and potassium ions] | journal = Tsitologiia | volume = 47 | issue = 6 | pages = 554–558 | year = 2005 | pmid = 16708849 | url = https://www.researchgate.net/publication/7072582 }} Additional studies have shown that lung tumors can be infiltrated by various populations of neutrophils.{{cite journal | vauthors = Zilionis R, Engblom C, Pfirschke C, Savova V, Zemmour D, Saatcioglu HD, Krishnan I, Maroni G, Meyerovitz CV, Kerwin CM, Choi S, Richards WG, De Rienzo A, Tenen DG, Bueno R, Levantini E, Pittet MJ, Klein AM | title = Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species | journal = Immunity | volume = 50 | issue = 5 | pages = 1317–1334.e10 | date = May 2019 | pmid = 30979687 | pmc = 6620049 | doi = 10.1016/j.immuni.2019.03.009 }} [144] => [145] => ==Video== [146] => [147] => File:S1-Polymorphonuclear Cells with Conidia in Liquid Media.ogv|A rapidly moving neutrophil can be seen taking up several [[conidia]] over an imaging time of 2 hours with one frame every 30 seconds. [148] => File:S15-Competitive Phagocytosis Assay in Collagen.ogg|A neutrophil can be seen here selectively taking up several [[Candida (genus)|''Candida'' yeast]]s ([[Fluorescent labelling|fluorescently labeled]] in green) despite several contacts with ''[[Aspergillus fumigatus]]'' conidia (unlabeled, white/clear) in a 3-D [[collagen]] matrix. Imaging time was 2 hours with one frame every 30 seconds. [149] => [150] => [151] => Neutrophils display highly directional amoeboid motility in infected footpad and phalanges. Intravital imaging was performed in the footpad path of LysM-eGFP mice 20 minutes after infection with ''[[Listeria monocytogenes]]''.{{cite journal | vauthors = Graham DB, Zinselmeyer BH, Mascarenhas F, Delgado R, Miller MJ, Swat W | title = ITAM signaling by Vav family Rho guanine nucleotide exchange factors regulates interstitial transit rates of neutrophils in vivo | journal = PLOS ONE | volume = 4 | issue = 2 | pages = e4652 | year = 2009 | pmid = 19247495 | pmc = 2645696 | doi = 10.1371/journal.pone.0004652 | veditors = Unutmaz D | doi-access = free | bibcode = 2009PLoSO...4.4652G }} [152] => [153] => ==Additional images== [154] => [155] => File:Illu blood cell lineage.jpg|Blood cell lineage [156] => File:Hematopoiesis (human) diagram en.svg|More complete lineages [157] => [158] => [159] => == See also == [160] => * [[List of distinct cell types in the adult human body]] [161] => [162] => == References == [163] => {{Reflist}} [164] => [165] => == External links == [166] => *[http://www.seattlechildrens.org/medical-conditions/heart-blood-conditions/neutropenia-symptoms/ Neutropenia Information] [167] => *[http://www.mdcalc.com/absolute-neutrophil-count-anc/ Absolute Neutrophil Count Calculator] [168] => *[http://pubs.rsc.org/en/content/articlelanding/2015/mt/c4mt00346b/ Neutrophil Trace Element Content and Distribution] [169] => {{Myeloid blood cells and plasma}} [170] => {{Lymphocytic immune system}} [171] => {{Authority control}} [172] => [173] => {{DEFAULTSORT:Neutrophil Granulocyte}} [174] => [[Category:Cell biology]] [175] => [[Category:Granulocytes]] [176] => [[Category:Phagocytes]] [177] => [[Category:Human cells]] [178] => [[Category:Articles containing video clips]] [] => )
good wiki

Neutrophil

Neutrophils are a type of white blood cell that play a crucial role in the immune response to infection. They are the most abundant type of white blood cell in the human body and are an essential part of the innate immune system.

More about us

About

They are the most abundant type of white blood cell in the human body and are an essential part of the innate immune system. Neutrophils are primarily responsible for engulfing and destroying pathogens, such as bacteria and fungi, through a process called phagocytosis. These cells are characterized by their multi-lobed nucleus and granular cytoplasm, which contains toxic substances and enzymes that are released to kill pathogens. Neutrophils are produced in the bone marrow and are released into the bloodstream, from where they can migrate to infected tissues through a process called chemotaxis. Neutrophils have a short lifespan and are constantly being produced to replace those that die during infection. They are also involved in the inflammation process, as their release of cytokines and other molecules helps recruit other immune cells to the site of infection. In addition, neutrophils have been implicated in various inflammatory diseases, such as rheumatoid arthritis and chronic obstructive pulmonary disease. Overall, neutrophils are critical for the body's defense against infection and their dysfunction can lead to impaired immune response and increased susceptibility to infections.

Expert Team

Vivamus eget neque lacus. Pellentesque egauris ex.

Award winning agency

Lorem ipsum, dolor sit amet consectetur elitorceat .

10 Year Exp.

Pellen tesque eget, mauris lorem iupsum neque lacus.

You might be interested in

Africa

Africa is the second-largest continent on Earth, covering about 30.

Antigen

An antigen is a substance that triggers an immune response in the body.

Apoptosis

Apoptosis, also known as programmed cell death, is a highly regulated form of cell death that occurs in multicellular organisms.

Bacteria

Bacteria are single-celled microorganisms that have a wide range of shapes and sizes.

Chemotaxis

Chemotaxis (from chemo- + taxis) is the movement of an organism or entity in response to a chemical stimulus.

Chemotherapy

Chemotherapy is a widely used treatment method in the field of oncology, aimed at treating cancer by administering drugs that kill rapidly dividing cells.

Chromatin

Chromatin is the material that makes up the chromosomes in eukaryotic cells.

Cytokine

Cytokines are small proteins that play a crucial role in cell signaling and immune responses in the human body.

Enzyme

Enzymes are macromolecular biological catalysts that accelerate chemical reactions.

Erythrocytes

Evolution

Evolution is a process that describes how living organisms have adapted and changed over time.

Histology

Histology is the study of the microscopic anatomy of cells and tissues of plants and animals.

Interleukin

Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells.

Leukemia

Leukemia is a type of cancer that affects the blood cells and bone marrow.

Lysozyme

Lysozyme is an enzyme found in various bodily secretions such as tears, saliva, mucus, and egg white.

Medication

Medication is a term used to describe any substance administered to a person or animal for the purpose of treating, curing, or preventing a medical condition.

Micrometre

A micrometre, also known as a micrometer, is a unit of length in the metric system.

Mitochondria

Ribosome

The Wikipedia page on Ribosome provides an in-depth description of this essential cellular component responsible for protein synthesis.

Sepsis

Sepsis is a life-threatening condition that occurs when the body's response to an infection damages its own tissues and organs.