Anti-inflammatory effects of prostaglandin E1: in vivo modulation of the formyl peptide chemotactic receptor on the rat neutrophil.
The local generation of chemotactic factors at sites of acute inflammation is thought to be responsible for the recruitment of polymorphonuclear leukocytes (PMN) from the intravascular compartment to the site of tissue injury (1). Many of these potent phlogistic mediators have also been shown to activate PMN resulting in degranulation of lysosomal granules with release of hydrolytic enzymes into the extracellular environment and the generation of superoxide anion (O2-) and other toxic metabolites (reviewed in Reference 2). Several in vitro studies have shown that treatment of PMN with specific prostaglandins will inhibit both soluble mediator- and particulate material-induced neutrophil lysosomal enzyme release and chemotaxis (3, 4). In vivo studies have demonstrated potent anti-inflammatory activity of prostaglandins of the E series (5-7). Systemic administration of prostaglandin E1 (PGE1) or its stable analog 15-(S)-15-methyl-PGE1 (15-M-PGE1) will inhibit neutrophil dependent immune complex tissue injury in a dose-dependent manner (8). In addition, i.v. infusion of PGE1 into humans has been shown to inhibit formyl-methionyl-leucyl-phenylalanine- (FMLP) induced lysosomal enzyme release from PMN (9). This study was undertaken to examine the effects of in vivo systemic treatment of rats with 15-M-PGE1 on FMLP-induced neutrophil lysosomal enzyme release and O2- secretion. As we will show, the modulation of FMLP-induced neutrophil function is correlated with a decrease in binding affinity for formyl-methionyl-leucyl-(3H)phenylalanine ((3H)-FMLP) to its specific receptor on the neutrophil plasma membrane. The data suggest a novel mechanism for the anti-inflammatory effects of prostaglandins of the E series.
D000527:Alprostadil; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D008247:Lysosomes / Q000201:enzymology; D009504:Neutrophils / Q000378:metabolism*; D011458:Prostaglandins E / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000032:analysis*; D044042:Receptors, Formyl Peptide; D013481:Superoxides / Q000378:metabolism; D014657:Vasculitis / Q000209:etiology / Q000276:immunology
D000893:Anti-Inflammatory Agents; D011458:Prostaglandins E; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D013481:Superoxides; D000527:Alprostadil