Neutrophil
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]
For organisms that grow in neutral pH environments, see Neutrophile.Neutrophil
They are formed from stem cells in the bone marrow and differentiated into subpopulations of neutrophil-killers and neutrophil-cagers. They are short-lived (between 5 and 135 hours, see § 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 bands). They form part of the polymorphonuclear cells family (PMNs) together with basophils and eosinophils.[3][4][5]
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.[6]
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,[7] and some cancers,[8][9] 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 interstitial space, following chemical signals such as interleukin-8 (IL-8), C5a, fMLP, leukotriene B4, and hydrogen peroxide (H2O2)[10] in a process called chemotaxis. They are the predominant cells in pus, accounting for its whitish/yellowish appearance.[11]
Neutrophils are recruited to the site of injury within minutes following trauma and are the hallmark of acute inflammation;[12] however, due to some pathogens being indigestible, they may not be able to resolve certain infections without the assistance of other types of immune cells.
Function[edit]
Chemotaxis[edit]
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.[26]
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 Rac1, hematopoietic Rac2, and RhoG GTPases of the Rho family and are required for cell motility. Rac-GTPases regulate cytoskeletal dynamics and facilitate neutrophils adhesion, migration, and spreading.[27] 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.[28]
Anti-microbial function[edit]
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]
Neutrophils are seen in a myocardial infarction at approximately 12–24 hours,[62] as seen in this micrograph.
![Neutrophils are seen in a myocardial infarction at approximately 12–24 hours,[62] as seen in this micrograph.](http://upload.wikimedia.org/wikipedia/commons/thumb/6/6c/Histopathology_of_neutrophil_infiltration_in_myocardial_infarction.jpg/267px-Histopathology_of_neutrophil_infiltration_in_myocardial_infarction.jpg)
![In stroke, they are beginning to infiltrate the infarcted brain after 6 to 8 hours.[63]](http://upload.wikimedia.org/wikipedia/commons/thumb/1/1e/Histopathology_of_thalamus_infarction_at_approximately_24_hours%2C_high_magnification%2C_annotated.jpg/325px-Histopathology_of_thalamus_infarction_at_approximately_24_hours%2C_high_magnification%2C_annotated.jpg)
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 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 lung injury.[54] 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.[55]
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.[56]
Hyperglycemia can lead to neutrophil dysfunction. Dysfunction in the neutrophil biochemical pathway myeloperoxidase as well as reduced degranulation are associated with hyperglycemia.[57]
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.[58] There is also new research tying ANC to myocardial infarction as an aid in early diagnosis.[59][60] Neutrophils promote ventricular tachycardia in acute myocardial infarction.[61]
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 diagnosis of myocardial infarction and stroke.
Just like phagocytes, pathogens may evade or infect neutrophils.[64] 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.[64]
Neutrophils can also serve as host cell for various parasites that infects them avoding phagocytosis, including:
Neutrophil antigens[edit]
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).[67]
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.[74]
Blood cell lineage
More complete lineages
