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Biological and Medical Sciences > Classification by Discipline > Immunology

Branch: Sci-Wiki
Type: General Knowledge
Intention: For Publication
Read/Write Permissions: Open Access
Authors :
08.10.2009 - Christopher Dyer  -  Sci-Mate   
08.10.2009 - Wendy Dawson   
05.05.2009 -   -  UVa   
24.04.2009 -   -  CHUL   

Neutrophils are short-lived (typically, less than 24 hrs in circulation), non-proliferating, terminally-differentiated granulocytes. They constitute the majority of circulating granulocytes and are, generally, the first cells to migrate toward inflammatory lesions (reviewed: (Furze and Rankin, 2008)) where they initiate host defense functions including the phagocytosis of invading microorganisms (Chon and Hirsch, 1960), the generation of oxygen-derived reactive agents (Babior et al., 1973) and the release of proteolytic enzymes (Reeves et al., 2002).


[edit] Immune Function

Frequent and severe infections in patients with defects in neutrophil function confirm their importance in host defense against infection (Holmes et al., 1967). They have also been shown to deliver an enormous destructive capacity that can cause significant tissue damage. Their unchecked activation has been associated with disease states such as ischemia, gram-negative bacterial sepsis and rheumatoid arthritis (reviewed, (Segal, 2005)). Elevated numbers of neutrophils in the synovial fluid of patients with arthritis support a role for these cells in joint destruction {reference needed}. Unraveling endogenous mechanisms which regulate and specifically limit neutrophil activation is, in turn, of interest in the context of identifying new and better therapeutic targets in the treatment of inflammatory diseases associated with unrepressed neutrophil activation.

[edit] Phagocytosis

Following the engulfment of a microorganism, Neutrophils release a respiratory oxidative burst to kill and break down the organism.

[edit] Cytokines

Neutrophils can respond to specific stimuli by synthesizing and releasing an array of chemical signals including: interleukin(IL)-1β, IL-1 receptor antagonist, IL-8, both granulocyte and macrophage colony-stimulating factors (CSF), inflammatory peptide (MIP)-1α and β, MIP-2, MIP-3, and interferon-α, each of which differentially contribute to the regulation of the inflammatory response (reviewed, (Kasama et al., 2005)). In addition, neutrophils synthesize antimicrobicidal proteins, extracellular matrix proteins fibronectin and thrombospondin (Kreis et al., 1989). Of interest, neutrophils constitute the main source of leukotriene (LT)B4 (Henderson and Klebanoff, 1983) and platelet-activating factor(PAF) {reference needed}, which are potent agonist and chemotactic agents for leukocytes, and can also generate significant amounts of prostaglandin (P)GE2 and thromboxane (TX)A2 {reference needed}.

[edit] Activation

The activation of neutrophils can be elicited by a large series of stimuli. However, several stimuli have been shown to activate neutrophils when "primed" by another chemical that on its own does not produce a detectable response {references needed}. This seems to be a mechanism suitable to trigger the appropriate defensive response where it is needed in a potentially damaging environment, since many of the most active neutrophil stimuli are derived from bacterial products, for instance, the formylated peptides and peptidoglycan, which explains the strong association of neutrophil infiltration with Gram positive bacterial infection.

[edit] References

Babior,B.M., Kipnes,R.S., and Curnutte,J.T. (1973). Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J. Clin. Invest 52, 741-744. Chon,Z.A. and Hirsch,J.G. (1960). The influence of phagocytosis on the intracellular distribution of granule-associated components of polymorphonuclear leucocytes. J. Exp. Med. 112, 1015-1022.
Furze,R.C. and Rankin,S.M. (2008). Neutrophil mobilization and clearance in the bone marrow. Immunology 125, 281-288. Henderson,W.R. and Klebanoff,S.J. (1983). Leukotriene production and inactivation by normal, chronic granulomatous disease and myeloperoxidase-deficient neutrophils. J. Biol. Chem. 258, 13522-13527.
Holmes,B., Page,A.R., and Good,R.A. (1967). Studies of the metabolic activity of leukocytes from patients with a genetic abnormality of phagocytic function. J. Clin. Invest 46, 1422-1432. Kasama,T., Miwa,Y., Isozaki,T., Odai,T., Adachi,M., and Kunkel,S.L. (2005). Neutrophil-derived cytokines: potential therapeutic targets in inflammation. Curr. Drug Targets. Inflamm. Allergy 4, 273-279.
Kreis,C., La,F.M., Menard,C., Paquin,R., and Beaulieu,A.D. (1989). Thrombospondin and fibronectin are synthesized by neutrophils in human inflammatory joint disease and in a rabbit model of in vivo neutrophil activation. J. Immunol. 143, 1961-1968. Reeves,E.P., Lu,H., Jacobs,H.L., Messina,C.G., Bolsover,S., Gabella,G., Potma,E.O., Warley,A., Roes,J., and Segal,A.W. (2002). Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature 416, 291-297. Segal,A.W. (2005). How neutrophils kill microbes custom essay. Annu. Rev. Immunol. 23, 197-223.

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