Regulation of platelet-activating factor (PAF) activity in human diseases by phospholipase A2 inhibitors, PAF acetylhydrolases, PAF receptor antagonists and free radical scavengers.
The aim of this review is to present recent findings indicating the likely involvement of platelet-activating factor (PAF) in human diseases, and possible ways of alleviating its harmful effects. PAF is a potent proinflammatory mediator and promotes adhesive interactions between leukocytes and endothelial cells, leading to transendothelial migration of leukocytes, by a process of juxtacrine intercellular signalling. This process leads to activation of leukocytes and the release of reactive oxygen radicals, lipid mediators, cytokines and enzymes. These reaction products subsequently contribute to the pathological features of various inflammatory diseases. The reactive oxygen radicals cause low density lipoprotein (LDL) oxidation which mediates the development of atherosclerosis. Oxidized LDL may damage cellular and subcellular membranes, leading to tissue injury and cell death. Among the therapeutic approaches considered are agents that inhibit/degrade proinflammatory mediators and thereby have anti-inflammatory and/or anti-atherogenic potential. These include inhibitors of phospholipase A2 activity, PAF-acetylhydrolases, PAF antagonists and free radical scavengers/antioxidants, the latter protecting against oxidized LDL-induced cytotoxicity.
Peplow
P V
PV
Department of Anatomy and Structural Biology, University of Otago, Dunedin, New Zealand.
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D007511:Ischemia / Q000188:drug therapy; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase