Neutrophil

A neutrophil is a granular, nucleated leukocyte , and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. They are quick to respond to infection challenge, often within hours. They are ephemeral cells, with a half-life on the order of 6 hours. Neutrophils are more associated with acute inflammatory response than macrophages, which are more involved in chronic inflammation. They normally make up 40% to 60% percent of all white cells; there may be an additional 0 to 3 percent of immature band neutrophils.

While their role has classically been associated with phagocytosis, a means of cell-mediated immune response in which they are attracted to targets via chemokines, more and more information has been accumulated about their role in releasing cytokines, especially interleukin 12 (IL-12). IL-12 encourages the production of interferon gamma (γ-interferon).

Precursors

In the creation of white cells, the original progenitor is the pluripotent stem cell. Under the influence of interleukins IL-1, IL-3, and IL-6, they form committed stem cells (i.e., progenitors). The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) causes differentiation into the neutrophils, with maturation to polymorphonuclear neutrophils via juvenile and band forms.

Immature forms of neutrophil are juvenile and band. Band neutrophils are immature cells, released by the bone marrow in response to demand. They have a single nucleus resembling a band, a sausage, or the letters C or U.

Polymorphonuclear neutrophil

The mature form of polymorphonuclear neutrophil (PMN) has a nucleus with three to five lobes connected by slender threads of chromatin. The average mature neutrophil has a diameter of about 13-15µm and a granulated cytoplasm.

Chemotaxis and migration

The neutrophil is able to chemotactically migrate to infected tissue, moving upstream against a concentration gradient of Interleukin-6, secreted by activated endothelial cells, mast cells and macrophages. When nearing the site of infection, the neutrophil will attach repeatedly to the endothelial blood vessel lining viz. selectins, thus dissipating kinetic energy. When the neutrophil has been slowed down enough, it will migrate from the blood vessel lumen to the infected tissue via an integrin-mediated pathway.

Activation

Because of their relative abundance compared to other leukocytes, neutrophil granulocytes are often the first to arrive at sites of new infection. The neutrophil granulocyte is activated through recognition of target molecules, viz the many different surface receptors the neutrophil expresses, some of which bind molecules that are unique to pathogens such as peptidoglycan, a component of bacterial cell walls. Apart from the innate ability to recognize potential pathogens, the neutrophil is also able to be activated by target-bound opsonins (antibodies), thus making the neutrophil a humoral effector cell.

Phagocytosis, degranulation and lysis

The neutrophil granulocyte is a phagocyte, capable of ingesting and lysing many pathogens. It does, however, not present antigens on its surface. Upon ingesting a pathogen, a phagosome is formed, into which oxidants and lytic enzymes are secreted.

The respiratory burst

In order to facilitate the lysis of ingested pathogens, the neutrophil synthesizes strong oxidants in what has been termed the respiratory burst, though it does not involve respiration. In the respiratory burst, the enzyme NADPH oxidase is activated, producing large amounts of superoxide, which spontaneously or catalyzed by superoxide dismutase dismutates to hydrogen peroxide, as per the following reaction:

$2{\mbox{O}}_{2}^{-}+2{\mbox{H}}_{2}{\mbox{O}}\rightarrow {\mbox{O}}_{2}+{\mbox{H}}_{2}{\mbox{O}}_{2}+2{\mbox{OH}}^{-}$

Hydrogen peroxide and chloride are subsequently converted by the enzyme myeloperoxidase to hypochlorous acid:

${\mbox{H}}_{2}{\mbox{O}}_{2}+2{\mbox{Cl}}^{-}\rightarrow 2{\mbox{HOCl}}$

Bromide is able to substitute for chloride in the reaction. Both hypochlorous and hypobromous acid are strong oxidants, and are directly able to kill the phagocytosed organisms.

Degranulation

Apart from phagocytic, oxidative lysis, the cytoplasm of the neutrophil contain many granulae, which contain soluble antimicrobial proteins, including lactoferrin, bactericidal/permeability increasing protein and defensins. These proteins generally confer their antimicrobial activity by increasing the permeability of bacterial, viral and fungal membranes, resulting in osmotic lysis. The exocytotic process in which these proteins are secreted to the surroundings is termed degranulation. This term is, however, most closely associated with the eosinophil granulocyte.