Neutrophil
Neutrophil | |
---|---|
platelets. Intra-cellular granules are visible in the cytoplasm (Giemsa stained). | |
Details | |
System | Immune system |
Function | Phagocytosis |
Identifiers | |
MeSH | D009504 |
TH | H2.00.04.1.02012 |
FMA | 62860 |
Anatomical terms of microanatomy] |
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 granulocytes and make up 40% to 70% of all white blood cells in humans.[1] They form an essential part of the innate immune system, with their functions varying in different animals.[2]
They are formed from
The name neutrophil derives from staining characteristics on
Neutrophils are a type of
Neutrophils are recruited to the site of injury within minutes following trauma and are the hallmark of acute inflammation;
Structure
When adhered to a surface, neutrophil granulocytes have an average diameter of 12–15
With the
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
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 African and Middle Eastern descent may have lower counts, which are still normal.[16] 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
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.[18] 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.[19][20]
Development
Life span
The average lifespan of inactivated human neutrophils in the circulation has been reported by different approaches to be between 5 and 135 hours.[21][22]
Upon activation, they marginate (position themselves adjacent to the blood vessel endothelium) and undergo
Neutrophils are much more numerous than the longer-lived
Neutrophils will be removed after
Function
Chemotaxis
Neutrophils undergo a process called
, 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.[26]
In leukocytes responding to a
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.[28]
Anti-microbial function
Being highly motile, neutrophils quickly congregate at a focus of infection, attracted by cytokines expressed by activated endothelium, mast cells, and macrophages. Neutrophils express[29] 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, and contain a broad range of proteins.[30] Neutrophils have three methods for directly attacking micro-organisms: phagocytosis (ingestion), degranulation (release of soluble anti-microbials), and generation of neutrophil extracellular traps (NETs).[31]
Phagocytosis
Neutrophils are
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.[32]
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.[33][34][35] 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.[36][37]
Degranulation
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 cells are polymorphonuclear leukocyte neutrophils with granules.[38]
Granule type | Protein |
Azurophilic granules (or "primary granules") |
bactericidal/permeability-increasing protein (BPI), defensins, and the serine proteases neutrophil elastase, Proteinase 3 and cathepsin G
|
Specific granules (or "secondary granules") | 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.
Tumor Associated Neutrophils
TANs can exhibit an elevated extracellular acidification rate when there is an increase in glycolysis levels.[52] 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.[52]
Clinical significance
Low neutrophil counts are termed
In
In
Hyperglycemia can lead to neutrophil dysfunction. Dysfunction in the neutrophil biochemical pathway myeloperoxidase as well as reduced degranulation are associated with hyperglycemia.[56]
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.[57] There is also new research tying ANC to myocardial infarction as an aid in early diagnosis.[58][59] Neutrophils promote ventricular tachycardia in acute myocardial infarction.[60]
In
-
Neutrophils are seen in a myocardial infarction at approximately 12–24 hours,[61] as seen in this micrograph.
Pathogen evasion and resistance
Just like phagocytes, pathogens may evade or infect neutrophils.[63] 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.[63]
Neutrophils can also serve as host cell for various parasites that infects them avoding phagocytosis, including:
- Leishmania major – uses neutrophils as vehicle to parasitize phagocytes[64]
- M. tuberculosis[65]
- M. leprae[65]
- Yersinia pestis[65]
- Chlamydia pneumoniae[65]
Neutrophil antigens
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 :
Subpopulations
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.[67][68][69][70][71] Additional studies have shown that lung tumors can be infiltrated by various populations of neutrophils.[72]
Video
-
A rapidly moving neutrophil can be seen taking up severalconidiaover an imaging time of 2 hours with one frame every 30 seconds.
-
A neutrophil can be seen here selectively taking up severalfluorescently labeled in green) despite several contacts with Aspergillus fumigatus conidia (unlabeled, white/clear) in a 3-D collagenmatrix. Imaging time was 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.[73]
Additional images
-
Blood cell lineage
-
More complete lineages
See also
References
- .
- S2CID 25619835.
- S2CID 22536645.
- ISBN 978-0-444-80020-6.
- S2CID 1590558.
- ISBN 978-1-260-57521-7. Retrieved 28 February 2023.
- PMID 20973949.
- S2CID 9415085.
- S2CID 9782495.
- PMID 22101434.
- ISBN 978-0-7020-4089-4.
- ^ Cohen S, Burns RC (2002). Pathways of the Pulp (8th ed.). St. Louis: Mosby. p. 465.
- PMID 25832493.
- ^ ISBN 978-0-8121-1094-4.
- S2CID 24750407.
- PMID 19180233.
- ^ ISBN 978-0-521-41698-6.
- 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
- PMID 18005717.
- ^ Kneller A (2007). "White blood cells are picky about sugar". Whitehead Institute. Retrieved 2013-08-09.
- S2CID 40113921.
- S2CID 909519.
- ^ ISBN 978-0-443-07001-3.
- PMID 35134856.
- PMID 19762280.
- ISBN 978-0-521-88729-8.
- PMID 29682742.
- PMID 23708969.
- PMID 18405381.
- ^ 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
- S2CID 8068543.
- PMID 15771570.
- S2CID 25253422.
- PMID 21844239.
- S2CID 27422510.
- PMID 12960399.
- PMID 28507953. Material was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
- PMID 13378597.
- PMID 6430792.
- S2CID 21628300.
- PMID 19876394.
- S2CID 22372863.
- PMID 34516771.
- PMID 34871043.
- S2CID 12887059.
- PMID 28363210.
- S2CID 2532741.
- PMID 20798043.
- PMID 22044575.
- S2CID 5368241.
- S2CID 216109364.
- ^ PMID 33753374.
- PMID 12223222.
- PMID 29922273.
- S2CID 3464945.
- PMID 24899891.
- S2CID 5499290.
- PMID 22328948.
- S2CID 37382677.
- PMID 36034743.
- PMID 31522288.)"
"This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/ Archived 2015-11-21 at the Wayback Machine - PMID 25806703.
- ^ PMID 29642066.
- PMID 19762280.
- ^ PMID 35003097.
- license.
- ^ .
- PMID 11517658.
- PMID 15174354.
- PMID 16708848.
- PMID 16708849.
- PMID 30979687.
- PMID 19247495.