Role for neutrophils

Romani L, Mencacci A, Cenci E, Del Sero G, Bistoni F, Puccetti P An iimnimoregulatory role for neutrophils in CD4+ T helper subset selection in mice with candidiasis. J Iimnunol 1997 158 2356-2364. 

Extensive studies on the tissue remodeling process in the endometrium have supported a role for neutrophils in angiogenesis. In 1994 Kelly et al. [34] examined the ability of endometrium explants and chorion cells in culture to synthesize and release lL-8. In the endometrium, the stage of the menstrual cycle did not affect lL-8 production, which was constant, and only high-dose progesterone reduced lL-8 levels. These observations suggested that the endometrium could be a target for neutrophil recruitment. 

Role for CXCR1 and CXCR2 in Tissue Infiltration of Neutrophils... 

C5a is inactivated by the myeloperoxidase-H202 system, which oxidises a methionine residue (Met 70) on the molecule group A streptococcal endo-proteinases also abolish chemotactic activity of C5a and related compounds. Neutrophil lysosomal enzymes (e.g. elastase and cathepsin G) also destroy C5a chemotactic activity, but as these proteases are inhibited by the serum antiproteinases, a -antiproteinase and a2-macroglobulin, the physiological role of neutrophilic proteases in the inactivation of C5a is questionable. Two chemotactic factor inactivators have been found in human serum an a-globulin that specifically and irreversibly inactivates C5-derived chemotactic factors, and a / -globulin that inactivates bacterial chemotactic factors. These activities are heat labile (destroyed by treatment at 56 °C for 30 min) and are distinct from those attributable to anaphylatoxin inactivator. An apparently specific inhibitor of C5-derived chemotactic activity has also been described in human synovial fluid and peritoneal fluid. This factor (molecular mass of 40 kDa) is heat stable and acts directly on C5a. 

These latter observations suggest a role for arachidonic acid as a genuine second messenger, and further work is necessary to assess if such a role exists during neutrophil activation. It has also been proposed that arachidonic acid may dissociate p21rac and GDI ( 5.3.2.3), thus allowing the small GTP-binding protein to interact with pAl-phox and p66-phox in the assembly of active NADPH oxidase complexes. 

The first experiments implicating a role for PLD activity in neutrophil function were performed by Cockcroft and colleagues (Cockcroft Stutchfield, 1989 Cockcroft, 1992) who measured phosphatidic acid accumulation in cells whose membrane phospholipids or ATP were radiolabelled. These experiments showed that phosphatidic acid accumulation during cell activation did not derive from DAG, but rather was directly generated from a phospholipid. Phosphatidic acid production from DAG (generated by PLC)... 

Steinbeck, M. J., Webb, D. S. A., Roth, J. A. (1989). Role for arachidonic acid metabolism and protein synthesis in recombinant bovine interferon- /induced activation of bovine neutrophils. J. Leuk. Biol. 46, 450-60. 

Myeloperoxidase is an extremely potent, antimicrobial protein that is present in neutrophils at up to 5% of the total cell protein. Its role in the killing of a wide range of bacteria, fungi, viruses, protozoa and mammalian cells (e.g. tumour cells) is well established from in vitro studies. It also plays an important role in the inactivation of toxins and the activation of latent proteases, as well as in other functions described in section 5.4.1. In view of this apparent central role in neutrophil function during host defence, one would think that any deficiencies in this enzyme would have disastrous consequences on the ability of the host to combat infections. Until the early 1980s, this key role for myeloperoxidase in host protection seemed substantiated by the extremely low incidence of reports of patients with deficiencies of this enzyme. Indeed, up to this time, only 15 cases from 12 families had been reported worldwide. Sometimes these patients were asymptomatic but often suffered Candida infections, particularly if their myeloperoxidase deficiency was also associated with diabetes mellitus. 

Dhein S, Schott M, Gottwald E, Muller A, Klaus W The contribution of neutrophils to reperfsuion arrhythmias and a possible role for antiadhesive pharmacological substances. Cardiovasc Res 1995a 30 881-888. 

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