3D rendering of a neutrophil.
|Anatomical terms of microanatomy|
Neutrophils (also known as neutrocytes) are the most abundant type of granulocytes and the most abundant (60% to 70%) type of white blood cells in most mammals. They form an essential part of the innate immune system, with their functions varying in different animals.
They are formed from stem cells in the bone marrow and differentiated into subpopulations of neutrophil-killers and neutrophil-cagers. They are short-lived and highly motile, or mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils (or bands). They form part of the polymorphonuclear cell family (PMNs) together with basophils and eosinophils.
The name neutrophil derives from staining characteristics on hematoxylin and eosin (H&E) histological or 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.
Neutrophils are a type of phagocyte and are normally found in the bloodstream. During the beginning (acute) phase of inflammation, particularly as a result of bacterial infection, environmental exposure, and some cancers, neutrophils are one of the first-responders of inflammatory cells to migrate towards the site of inflammation. They migrate through the blood vessels, then through interstitial tissue, following chemical signals such as Interleukin-8 (IL-8), C5a, fMLP, Leukotriene B4 and H2O2 in a process called chemotaxis. They are the predominant cells in pus, accounting for its whitish/yellowish appearance.
Neutrophils are recruited to the site of injury within minutes following trauma and are the hallmark of acute inflammation; however, due to some pathogens being indigestible, they can be unable to resolve certain infections without the assistance of other types of immune cells.
When adhered to a surface, neutrophil granulocytes have an average diameter of 12–15 micrometers (µm) in peripheral blood smears. In suspension, human neutrophils have an average diameter of 8.85 µm.
With the eosinophil and the basophil, they form the class of polymorphonuclear cells, named for the nucleus' multilobulated shape (as compared to lymphocytes and monocytes, 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.:168 In the cytoplasm, the Golgi apparatus is small, mitochondria and ribosomes are sparse, and the rough endoplasmic reticulum is absent.:170 The cytoplasm also contains about 200 granules, of which a third are azurophilic.:170
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 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.
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 x 109/L is a standard normal range. People of African and Middle Eastern descent may have lower counts, which are still normal. A report may divide neutrophils into segmented neutrophils and bands.
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 antigens.
Neutrophils have a preference to engulf refined carbohydrates (from ingested glucose, fructose, sucrose, honey and orange juice) over bacteria. In 1973 Sanchez et al. found that the neutrophil phagocytic capacity to engulf bacteria is affected when simple sugars are digested, and that fasting strengthens the neutrophils' phagocytic capacity to engulf bacteria. However, the digestion of normal starches has no effect. It was concluded that the function, and not the number, of phagocytes in engulfing bacteria was altered by the ingestion of sugars. In 2007 researchers at the Whitehead Institute of Biomedical Research found that given a selection of sugars, neutrophils engulf some types of sugar preferentially.
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 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 evolutionary adaptation. The short lifetime of neutrophils minimizes propagation of those pathogens that parasitize phagocytes because the more time such parasites spend outside a host 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 tissues, their short life limits damage to the host during inflammation.
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, C5a, and Leukotriene B4, which these cells use to direct the path of their migration.
Neutrophils have a variety of specific receptors, including ones for complement, cytokines like interleukins and IFN-γ, chemokines, lectins, and other proteins. They also express receptors to detect and adhere to endothelium and Fc receptors for opsonin.
In leukocytes responding to a chemoattractant, the cellular polarity is regulated by activities of small Rho guanosine triphosphatases (Rho GTPases) and the phosphoinositide 3-kinases (PI3Ks). In neutrophils, lipid products of PI3Ks regulate activation of Rho GTPases and are required for cell motility. 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.
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.
Being highly motile, neutrophils quickly congregate at a focus of infection, attracted by cytokines expressed by activated endothelium, mast cells, and macrophages. Neutrophils express and release cytokines, which in turn amplify inflammatory reactions by several other cell types.
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. Neutrophils have three methods for directly attacking micro-organisms: phagocytosis (ingestion), degranulation (release of soluble anti-microbials), and generation of neutrophil extracellular traps (NETs).
Neutrophils are phagocytes, capable of ingesting microorganisms or particles. For targets to be recognized, they must be coated in opsonins—a process known as antibody opsonization. They can internalize and kill many microbes, 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.
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 dismutases (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.
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. Thus, some bacteria—and those that are predominantly intracellular pathogens—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.
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.
|Azurophilic granules (or "primary granules")||Myeloperoxidase, bactericidal/permeability-increasing protein (BPI), defensins, and the serine proteases neutrophil elastase and cathepsin G|
|Specific granules (or "secondary granules")||Alkaline phosphatase, lysozyme, NADPH oxidase, collagenase, lactoferrin, histaminase, and cathelicidin|
|Tertiary granules||Cathepsin, gelatinase and collagenase|
Neutrophil extracellular traps
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. These neutrophil extracellular traps (NETs) comprise a web of fibers composed of chromatin and serine proteases  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. 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. In addition, NETs are known to exhibit pro-thrombotic effects both in vitro and in vivo.
Low neutrophil counts are termed neutropenia. This can be 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 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.
In alpha 1-antitrypsin deficiency, the important neutrophil enzyme elastase is not adequately inhibited by alpha 1-antitrypsin, leading to excessive tissue damage in the presence of inflammation – the most prominent one being pulmonary emphysema. Negative effects of elastase has been also shown in cases when the neutrophils are excessively activated (in otherwise healthy individual) and release the enzyme in extracellular space. Unregulated activity of neutrophil elastase can lead to disruption of pulmonary barrier showing symptoms corresponding with acute lung injury. The enzyme also influences activity of macrophages by cleaving their toll-like receptors (TLRs) and downregulating cytokine expression by inhibiting nuclear translocation of NF-κB.
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 response and causes attacks of fever, arthralgia, peritonitis, and – eventually – amyloidosis.
Decreases in neutrophil function have been linked to hyperglycemia. Dysfunction in the neutrophil biochemical pathway myeloperoxidase as well as reduced degranulation are associated with hyperglycemia.
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. There is also new research tying ANC to myocardial infarction as an aid in early diagnosis.
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).
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. Additional studies have shown that lung tumors can be infiltrated by various populations of neutrophils.
A rapidly moving neutrophil can be seen taking up several conidia over an imaging time of 2 hours with one frame every 30 seconds.
 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.
- Ermert D, Niemiec MJ, Röhm M, Glenthøj A, Borregaard N, Urban CF (August 2013). "Candida albicans escapes from mouse neutrophils". Journal of Leukocyte Biology. 94 (2): 223–36. doi:10.1189/jlb.0213063. PMID 23650619.
- Witko-Sarsat V, Rieu P, Descamps-Latscha B, Lesavre P, Halbwachs-Mecarelli L (May 2000). "Neutrophils: molecules, functions and pathophysiological aspects". Laboratory Investigation; A Journal of Technical Methods and Pathology. 80 (5): 617–53. doi:10.1038/labinvest.3780067. PMID 10830774.
- Klebanoff SJ, Clark RA (1978). The Neutrophil: Function and Clinical Disorders. Elsevier/North-Holland Amsterdam. ISBN 978-0-444-80020-6.
- Nathan C (March 2006). "Neutrophils and immunity: challenges and opportunities". Nature Reviews. Immunology. 6 (3): 173–82. doi:10.1038/nri1785. PMID 16498448.
- Jacobs L, Nawrot TS, de Geus B, Meeusen R, Degraeuwe B, Bernard A, Sughis M, Nemery B, Panis LI (October 2010). "Subclinical responses in healthy cyclists briefly exposed to traffic-related air pollution: an intervention study". Environmental Health. 9 (64): 64. doi:10.1186/1476-069X-9-64. PMC 2984475. PMID 20973949.
- Waugh DJ, Wilson C (November 2008). "The interleukin-8 pathway in cancer". Clinical Cancer Research. 14 (21): 6735–41. doi:10.1158/1078-0432.CCR-07-4843. PMID 18980965.
- De Larco JE, Wuertz BR, Furcht LT (August 2004). "The potential role of neutrophils in promoting the metastatic phenotype of tumors releasing interleukin-8". Clinical Cancer Research. 10 (15): 4895–900. doi:10.1158/1078-0432.CCR-03-0760. PMID 15297389.
- Yoo SK, Starnes TW, Deng Q, Huttenlocher A (November 2011). "Lyn is a redox sensor that mediates leukocyte wound attraction in vivo". Nature. 480 (7375): 109–12. Bibcode:2011Natur.480..109Y. doi:10.1038/nature10632. PMC 3228893. PMID 22101434.
- Barer MR (2012). "The natural history of infection". Medical Microbiology. Elsevier. pp. 168–173. doi:10.1016/b978-0-7020-4089-4.00029-9. ISBN 978-0-7020-4089-4.
- Cohen S, Burns RC (2002). Pathways of the Pulp (8th ed.). St. Louis: Mosby. p. 465.
- 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 (June 2015). "Trace element landscape of resting and activated human neutrophils on the sub-micrometer level". Metallomics. 7 (6): 996–1010. doi:10.1039/c4mt00346b. PMID 25832493.
- Zucker-Franklin D, Greaves MF, Grossi CE, Marmont AM (1988). "Neutrophils". Atlas of Blood Cells: Function and Pathology. 1 (2nd ed.). Philadelphia: Lea & Ferbiger. ISBN 978-0-8121-1094-4.
- 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 (January 2009). "Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene". PLOS Genetics. 5 (1): e1000360. doi:10.1371/journal.pgen.1000360. PMC 2628742. PMID 19180233.
- Edwards SW (1994). Biochemistry and physiology of the neutrophil. Cambridge University Press. p. 6. ISBN 978-0-521-41698-6.
- Sanchez A, Reeser JL, Lau HS, Yahiku PY, Willard RE, McMillan PJ, Cho SY, Magie AR, Register UD (November 1973). "Role of sugars in human neutrophilic phagocytosis". The American Journal of Clinical Nutrition. 26 (11): 1180–4. doi:10.1093/ajcn/26.11.1180. PMID 4748178.
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
- Rubin-Bejerano I, Abeijon C, Magnelli P, Grisafi P, Fink GR (July 2007). "Phagocytosis by human neutrophils is stimulated by a unique fungal cell wall component". Cell Host & Microbe. 2 (1): 55–67. doi:10.1016/j.chom.2007.06.002. PMC 2083279. PMID 18005717.
- Kneller A (2007). "White blood cells are picky about sugar". Whitehead Institute. Retrieved 2013-08-09.
- Tak T, Tesselaar K, Pillay J, Borghans JA, Koenderman L (October 2013). "What's your age again? Determination of human neutrophil half-lives revisited". Journal of Leukocyte Biology. 94 (4): 595–601. doi:10.1189/jlb.1112571. PMID 23625199.
- Pillay J, den Braber I, Vrisekoop N, Kwast LM, de Boer RJ, Borghans JA, Tesselaar K, Koenderman L (July 2010). "In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days". Blood. 116 (4): 625–7. doi:10.1182/blood-2010-01-259028. PMID 20410504.
- Wheater PR, Stevens A (2002). Wheater's basic histopathology: a colour atlas and text. Edinburgh: Churchill Livingstone. ISBN 978-0-443-07001-3.
- Serhan CN, Ward PA, Gilroy DW (2010). Fundamentals of Inflammation. Cambridge University Press. pp. 53–54. ISBN 978-0-521-88729-8.
- Lämmermann T, Afonso PV, Angermann BR, Wang JM, Kastenmüller W, Parent CA, Germain RN (June 2013). "Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo". Nature. 498 (7454): 371–5. Bibcode:2013Natur.498..371L. doi:10.1038/nature12175. PMC 3879961. PMID 23708969.
- Ear T, McDonald PP (April 2008). "Cytokine generation, promoter activation, and oxidant-independent NF-kappaB activation in a transfectable human neutrophilic cellular model". BMC Immunology. 9: 14. doi:10.1186/1471-2172-9-14. PMC 2322942. PMID 18405381.
- Hickey MJ, Kubes P (May 2009). "Intravascular immunity: the host-pathogen encounter in blood vessels". Nature Reviews. Immunology. 9 (5): 364–75. doi:10.1038/nri2532. PMID 19390567.
- Segal AW (2005). "How neutrophils kill microbes". Annual Review of Immunology. 23 (5): 197–223. doi:10.1146/annurev.immunol.23.021704.115653. PMC 2092448. PMID 15771570.
- Simons MP, et al. (2006). "Neisseria gonorrhoeae delays the onset of apoptosis in polymorphonuclear leukocytes". Cell Microbiol. 8 (11): 1780–90. doi:10.1111/j.1462-5822.2006.00748.x. PMID 16803582.
- Chen A, et al. (2004). "Neisseria gonorrhoeae-mediated inhibition of apoptotic signalling in polymorphonuclear leukocytes". Infect. Immun. 79 (11): 4447–58. doi:10.1128/IAI.01267-10. PMC 3257915. PMID 21844239.
- van Zandbergen G, et al. (2004). "Chlamydia pneumoniae multiply in neutrophil granulocytes and delay their spontaneous apoptosis". J. Immunol. 172 (3): 1768–76. doi:10.4049/jimmunol.172.3.1768. PMID 14734760.
- Kobayashi SD, et al. (2003). "Bacterial pathogens modulate an apoptosis differentiation program in human neutrophils". Proc. Natl. Acad. Sci. U.S.A. 100 (19): 10948–10953. doi:10.1073/pnas.1833375100. PMC 196908. PMID 12960399.
- Scott DK, et al. (2017). "Influence of Microbes on Neutrophil Life and Death". Front Cell Infect Microbiol. 7 (159): 159. doi:10.3389/fcimb.2017.00159. PMC 5410578. PMID 28507953. Material was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
- Ringel EW, Soter NA, Austen KF (August 1984). "Localization of histaminase to the specific granule of the human neutrophil". Immunology. 52 (4): 649–58. PMC 1454675. PMID 6430792.
- Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A (March 2004). "Neutrophil extracellular traps kill bacteria". Science. 303 (5663): 1532–5. Bibcode:2004Sci...303.1532B. doi:10.1126/science.1092385. PMID 15001782.
- Urban CF, Ermert D, Schmid M, Abu-Abed U, Goosmann C, Nacken W, Brinkmann V, Jungblut PR, Zychlinsky A (October 2009). "Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans". PLOS Pathogens. 5 (10): e1000639. doi:10.1371/journal.ppat.1000639. PMC 2763347. PMID 19876394.
- 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 (April 2007). "Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood". Nature Medicine. 13 (4): 463–9. doi:10.1038/nm1565. PMID 17384648.
- Gupta AK, Hasler P, Holzgreve W, Hahn S (June 2007). "Neutrophil NETs: a novel contributor to preeclampsia-associated placental hypoxia?" (PDF). Seminars in Immunopathology. 29 (2): 163–7. doi:10.1007/s00281-007-0073-4. PMID 17621701.
- Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD, Wrobleski SK, Wakefield TW, Hartwig JH, Wagner DD (September 2010). "Extracellular DNA traps promote thrombosis". Proceedings of the National Academy of Sciences of the United States of America. 107 (36): 15880–5. Bibcode:2010PNAS..10715880F. doi:10.1073/pnas.1005743107. PMC 2936604. PMID 20798043.
- Brill A, Fuchs TA, Savchenko AS, Thomas GM, Martinod K, De Meyer SF, Bhandari AA, Wagner DD (January 2012). "Neutrophil extracellular traps promote deep vein thrombosis in mice". Journal of Thrombosis and Haemostasis. 10 (1): 136–44. doi:10.1111/j.1538-7836.2011.04544.x. PMC 3319651. PMID 22044575.
- Borissoff JI, ten Cate H (September 2011). "From neutrophil extracellular traps release to thrombosis: an overshooting host-defense mechanism?". Journal of Thrombosis and Haemostasis. 9 (9): 1791–4. doi:10.1111/j.1538-7836.2011.04425.x. PMID 21718435.
- Kawabata K, Hagio T, Matsuoka S (September 2002). "The role of neutrophil elastase in acute lung injury". European Journal of Pharmacology. 451 (1): 1–10. doi:10.1016/S0014-2999(02)02182-9. PMID 12223222.
- Domon H, Nagai K, Maekawa T, Oda M, Yonezawa D, Takeda W, Hiyoshi T, Tamura H, Yamaguchi M, Kawabata S, Terao Y (2018). "Neutrophil Elastase Subverts the Immune Response by Cleaving Toll-Like Receptors and Cytokines in Pneumococcal Pneumonia". Frontiers in Immunology. 9: 732. doi:10.3389/fimmu.2018.00732. PMC 5996908. PMID 29922273.
- Ozen S (July 2003). "Familial mediterranean fever: revisiting an ancient disease". European Journal of Pediatrics. 162 (7–8): 449–454. doi:10.1007/s00431-003-1223-x. PMID 12751000.
- Xiu F, Stanojcic M, Diao L, Jeschke MG (8 May 2014). "Stress hyperglycemia, insulin treatment, and innate immune cells". International Journal of Endocrinology. 2014: 486403. doi:10.1155/2014/486403. PMC 4034653. PMID 24899891.
- Al-Gwaiz LA, Babay HH (2007). "The diagnostic value of absolute neutrophil count, band count and morphologic changes of neutrophils in predicting bacterial infections". Medical Principles and Practice. 16 (5): 344–7. doi:10.1159/000104806. PMID 17709921.
- Khan HA, Alhomida AS, Sobki SH, Moghairi AA, Koronki HE (2012). "Blood cell counts and their correlation with creatine kinase and C-reactive protein in patients with acute myocardial infarction". International Journal of Clinical and Experimental Medicine. 5 (1): 50–5. PMC 3272686. PMID 22328948.
- Basili S, Di Francoi M, Rosa A, Ferroni P, Diurni V, Scarpellini MG, Bertazzoni G (April 2004). "Absolute neutrophil counts and fibrinogen levels as an aid in the early diagnosis of acute myocardial infarction". Acta Cardiologica. 59 (2): 135–40. doi:10.2143/ac.59.2.2005167. PMID 15139653.
- 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 (September 2013). "Genotyping of human neutrophil antigens (HNA) from whole genome sequencing data". BMC Medical Genomics. 6 (1): 31. doi:10.1186/1755-8794-6-31. PMC 3849977. PMID 24028078.
- Ignatov DY (2012). Functional heterogeneity of human neutrophils and their role in peripheral blood leukocyte quantity regulation (PhD). Donetsk National Medical University. doi:10.13140/RG.2.2.35542.34884.
- Gerasimov IG, Ignatov DI (2001). "[Functional heterogenicity of human blood neutrophils: generation of oxygen active species]". Tsitologiia. 43 (5): 432–6. PMID 11517658.
- Gerasimov IG, Ignatov DI (2004). "[Neutrophil activation in vitro]". Tsitologiia. 46 (2): 155–8. PMID 15174354.
- Gerasimov IG, Ignatov DI, Kotel'nitskiĭ MA (2005). "[Nitroblue tetrazolium reduction by human blood neutrophils. I. The influence of pH]". Tsitologiia. 47 (6): 549–53. PMID 16708848.
- Gerasimov IG, Ignatov DI (2005). "[Nitroblue tetrazolium reduction by human blood neutrophils. II. The influence of sodium and potassium ions]". Tsitologiia. 47 (6): 554–8. PMID 16708849.
- 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 (May 2019). "Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species". Immunity. 50 (5): 1317–1334.e10. doi:10.1016/j.immuni.2019.03.009. PMC 6620049. PMID 30979687.
- Graham DB, Zinselmeyer BH, Mascarenhas F, Delgado R, Miller MJ, Swat W (2009). Unutmaz D (ed.). "ITAM signaling by Vav family Rho guanine nucleotide exchange factors regulates interstitial transit rates of neutrophils in vivo". PLOS One. 4 (2): e4652. Bibcode:2009PLoSO...4.4652G. doi:10.1371/journal.pone.0004652. PMC 2645696. PMID 19247495.