Platelet-activating factor-induced enhancement of superoxide anion generation in guinea-pigs

We studied whether platelet-activating factor (PAF) enhances superoxide anion (O2-) generation in guinea-pigs. The production of O2- was assayed by chemiluminescence, using a Cypridina luciferin analog as a highly sensitive and specific probe for O2-. I.v. administered PAF significantly enhanced phorbol myristate acetate- or N-formyl-methionyl-leucyl-phenylalanine-induced O2- generation by guinea-pig alveolar macrophages or by polymorphonuclear leukocytes in a dose-dependent manner. The priming effect of PAF on O2- generation was maximal in cells harvested 5 min after administration of PAF. These responses were completely inhibited by administration of WEB 2086, a specific PAF receptor antagonist, or ONO-3708, a specific thromboxane A2 receptor antagonist, suggesting that the effects were mediated through the PAF receptor and thromboxane A2 generation. PAF might contribute to airway inflammation by enhancing O2- formation in addition to exerting other effects such as smooth muscle contraction or microvascular leakage.