Platelet-Activating Factor Amplifies Tumour Necrosis Factor-Induced Superoxide Generation by Human Neutrophils
Inflammation is usually a tightly controlled process which confines tissue damage, prevents infection and assists in cellular regeneration. However, if the inflammatory response becomes unregulated, this normally beneficial local event may escalate into a wider malignant activity involving endothelial injury, excessive cell infiltration and vascular leakage. Such phenomena may underlie the microcirculatory damage observed in shock, sepsis, asthma, ischemia and graft rejection. Neutrophils (PMN) appear to play a particularly important role in inflammation and inflammatory disorders (1). In the inflammatory microenvironment, neutrophils become activated by various agonists, adhere to the endothelial surface and release lysosomal proteases. Activated PMN also undergo a “respiratory burst”, which results in the reduction of molecular oxygen to superoxide (1). These toxic products released by PMN are capable of eliciting severe endothelial damage.
KeywordsSuperoxide Production Superoxide Generation Tumour Necrosis Factor Production Superoxide Release Tumour Necrosis Factor Concentration
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- 2.P. Braquet, L. Touqui, T.S. Shen, and B.B. Vargaftig, 1987, Perspectives in platelet-activating factor research. Pharmacol Reviews., 39:97.Google Scholar
- 10.P. Braquet, 1987, The Ginkgolides : potent platelet-activating factor antagonists isolated from Ginkgo Biloba L. Drugs of the Future, 12:643.Google Scholar
- 11.C. Broquet, and P. Braquet, 1988, Compositions thérapeutiques à base de nouveaux aminoacylates dacétal du glycerol. Fr. Patent. Nº 2.616.326.Google Scholar
- 12.F.H. Valone, and L.B. Epstein, 1988, Biphasic platelet-activating factor synthesis by human monocytes stimulated with interleukin 1 beta (IL 1), tumor necrosis factor (TNF) or gamma interferon (IFN). J. Immunol., 11:3945.Google Scholar
- 13.M. Rola-Pleszczynski, 1988, Priming of human monocytes with PAF augments their production of tumour necrosis factor in response to interleukin 1. J. Lipid Mediators., in press.Google Scholar
- 15.M.L. Blank, T.C. Lee, V. Fitzgerald, and F. Snyder, 1981, Anti-hypertensive activity of an alkyl ether analog of phosphatidylcholine. Biochem. Biophys. Res. Commun., 29: 2472.Google Scholar
- 16.H. Heuer, and G. Letts, 1989, Priming of effects of PAF in vivo by tumor necrosis factor and endotoxin. J. Lipid Mediators., in press.Google Scholar