Production by neutrophils

Williams, J.G. and Hallett, M.B. (1989).Effect of sulphasalazine and its active metabolite, 5-aminosalicylic acid, on toxic oxygen metabolite production by neutrophils. Gut 30, 1581-1587. 

The antiulcer agent rebamipide ((2-(4-chlorobenzoy-lamino)-3-[2(lH)-quinolinon-4-yl]propionic acid) dose-dependently decreased hydroxyl radical signal generated by the Fenton reaction in an e.s.r. study. Rebamipide is active as a hydroxyl radical scavenger and inhibitor of superoxide production by neutrophils (Yoshikawa etal., 1993). 

IFN-y has therapeutic activity in chronic granulomatous disease (CGD).34 In CGD, the mechanism of therapeutic activity by IFN-y appears to be associated with enhanced phagocytic oxidase activity and increased superoxide production by neutrophils. However,... 

Incubation periods in excess of 2 h were required before this activity was detected in cell-free supernatants. More recently, the use of cDNA probing of Northern transfers (to detect specific mRNA levels), the use of ELISA techniques (to detect protein levels immunologically) and the development of more specific bioassays (culture techniques in which a biomolecule stimulates proliferation in a particular cell line) have resulted in a more thorough analysis of IL-1 production by neutrophils. IL-1 is only poorly expressed in blood neutrophils because mRNA for this cytokine is detectable only at very low levels (if at all), and protein production is usually below the level of detection of most assays. However, exposure of neutrophils to lipopolysaccharide (LPS), or to cytokines such as GM-CSF, TNF or IL-1 itself, results in a rapid but transient increase in IL-1 expression. 

IL-6 induces terminal maturation of B cells, promotes the growth of hy-bridoma/myeloma cells and T cells, and acts upon haematopoietic progenitors in synergy with IL-1 and IL-3. It also induces the production of acute-phase proteins by liver cells. In addition to its production by neutrophils, IL-6 is also synthesised by monocytes, T and B cells, fibroblasts, cardiac myxoma cells, some bladder carcinomas, cervical cancer cells and glioblastomas. Stimulated neutrophils generate about ten times less IL-6 (on a per-cell basis) than do monocytes. 

Figure 7.11. Cytokine production by neutrophils. This scheme shows the major cytokines produced by primed neutrophils, as well as some of the major biological effects of these neutrophil-derived cytokines.

G-CSF activates neutrophils, transforming them into cells capable of respiratory burst and release of secretory granules. It also modulates the expression of adhesion molecules on neutrophils as well as CD1 lb/CD18 and plasma elastase antigen levels. G-CSF induces proliferation of endothelial cells, phagocytic activity of neutrophils, reactive oxygen intermediate production by neutrophils and antibody-dependent cellular toxicity by neutrophils. 

Superoxide Ofj production by neutrophils and macrophages is part of the host defenses against microorganisms. PLD has been imphcated in this response because agents that elicit O2 formation also activate PLD [162-164]. In addition, in vitro experiments showed that PA elicited NADPH-dependent O2 formation in neutrophil extracts or intact neutrophils [165, 166]. Some studies also showed a high correlation between O2 production and PA accumulation in neutrophils stimulated with FMLP [167]. Furthermore, treatment of these cells with ethanol decreased both PA formation and O2 generation. 

Most PI3Ks (including Class 1 and Ig) are inhibited by a fungal toxin, wortmannin, and the structurally unrelated inhibitor LY294002. These compounds are potent inhibitors of chemoattractant-induced degranulation and oxidant production by neutrophils although phospholipase C activation and the cytosolic calcium increase are not... 

Oxidant production by neutrophils and changes in oxidant-antioxidant levels have long been suspected as contributing to airway inflammation and bronchiectasis in cystic fibrosis, although proving this suspicion has turned out to be a... 

Both drugs that inhibit oxygen metabolite production by neutrophils and alveolar macrophages (e.g. pentoxifylline) and radical scavengers (e.g. 

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