Neutrophil

Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in different animals. They are also known as neutrocytes, heterophils or polymorphonuclear leukocytes.
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 mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils. They form part of the polymorphonuclear cells family together with basophils and eosinophils.
The name neutrophil derives from staining characteristics on hematoxylin and eosin 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 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 toward the site of inflammation. They migrate through the blood vessels and then through interstitial space, following chemical signals such as interleukin-8, C5a, fMLP, leukotriene B4, and hydrogen peroxide 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. They not only play a central role in combating infection but also contribute to pain in the acute period by releasing pro-inflammatory cytokines and other mediators that sensitize nociceptors, leading to heightened pain perception. 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.

Structure

When adhered to a surface, neutrophil granulocytes have an average diameter of 12–15 micrometers 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. 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. Up to 17% of female human neutrophil nuclei have a drumstick-shaped appendage which contains the inactivated X chromosome. In the cytoplasm, the Golgi apparatus is small, mitochondria and ribosomes are sparse, and the rough endoplasmic reticulum is absent. The cytoplasm also contains about 200 granules, of which a third are azurophilic.
Neutrophils will show increasing segmentation 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 the human body ; they account for approximately 50–70% of all white blood cells. 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. 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.

Reaction to sugars

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. 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.

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.
Upon activation, they marginate 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.
The distribution ratio of neutrophils in bone marrow, blood and connective tissue is 28:1:25.
Neutrophils are much more numerous than the longer-lived monocyte/macrophage phagocytes. A pathogen 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 will be removed after phagocytosis of pathogens by macrophages. PECAM-1 and phosphatidylserine on the cell surface are involved in this process.

Function

Chemotaxis

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, interferon gamma, 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 the complement system, 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 Ras or Rho guanosine triphosphatases and the phosphoinositide 3-kinases. 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. Ras-GTPases and Rac-GTPases regulate cytoskeletal dynamics and facilitate neutrophils adhesion, migration, and spreading. 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.

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 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. Neutrophils have three methods for directly attacking microorganisms: phagocytosis, degranulation, and generation of neutrophil extracellular traps.

Phagocytosis

Neutrophils are phagocytes, capable of ingesting microorganisms or particles. For targets to be recognized, they must be coated in opsoninsa 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, to hydrogen peroxide, which is then converted to hypochlorous acid, 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 bacteriaand those that are predominantly intracellular pathogenscan extend the neutrophil lifespan by disrupting the normal process of spontaneous apoptosis and/or PICD. 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.