Effect of a platelet-activating factor antagonist, WEB 2086, on inhibition of active oxygen generation in human polymorphonuclear leukocytes.

Abstract

We investigated the effect of WEB 2086, 3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo- [4,3-a][1,4]-diazepin-2-yl]-1-(4-morpholinyl)-1-propanone, an antagonist of platelet-activating factor, on the generation of active oxygen by human polymorphonuclear leukocytes. This agent inhibited the production of oxidative metabolites by these cells following stimulation by opsonized zymosan and formyl-methionyl-leucyl-phenylalanine in a time-dependent fashion. To determine whether it would directly inhibit the production of oxygen metabolites by these cells, they were preincubated with WEB 2086 and washed prior to stimulation. WEB 2086 was found to directly inhibit the generation of active oxygen metabolites by these cells. WEB 2086 may be a scavenger of active oxygen metabolites since it rapidly inhibited the production of active oxygen metabolites by these cells. It also directly affected the scavenging of active oxygen metabolites that were generated by the opsonized zymosan-stimulated human polymorphonuclear leukocytes. This action of WEB 2086 was also noted to be exerted against hydroxyl radicals and superoxide anions produced biochemically by an electron spin resonance spectrometer. It thus follows that WEB 2086 may inhibit the generation of active oxygen metabolites by human polymorphonuclear leukocytes and directly influence the scavenging of these metabolites.