Generation of a biologically active lipid from arachidonic acid by exposure to a superoxide-generating system.

A biologically active lipid was produced by incubating arachidonic acid with a superoxide-generating system consisting of xanthine oxidase plus acetaldehyde. The lipid proved to be a potent chemoattractant for human polymorphonuclear leukocytes and also was capable of inhibiting platelet aggregation induced either by arachidonic acid or by the endoperoxide analog, 9,11-azoprostanoid III. Generation of the biologically active lipid required the presence of all of the reactants, was time-dependent and could be inhibited by scavengers of superoxide, hydroxyl radicals, and singlet oxygen. Silica gel thin-layer radiochromatography demonstrated a single peak with biological activity, distinct from unaltered arachidonic acid. The biologically active lipid was most likely generated by the peroxidation of arachidonic acid. Biologically active products of arachidonic acid formed nonenzymatically by the action of oxygen-derived free radicals may play important roles in the mediation and modulation of inflammatory responses.