PLATELET-ACTIVATING-FACTOR MAY PARTICIPATE IN SIGNAL TRANSDUCTION PROCESSES IN RABBIT LEUKOCYTES

The bacterial chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (fMLP), induces the generation of platelet-activating factor (PAF), the mobilization of arachidonic acid and generation of superoxide anion (O2-) in rabbit polymorphonuclear leukocytes (PMNs). The PAF receptor antagonists, WEB 2086 (10-100-mu-M) and CV 6209 (1-10-mu-M), reduced the mobilization of arachidonic acid and the O2- generation in response to fMLP but not that in response to A23187. Pretreatment of PMNs with the phospholipase A2 inhibitor, chloroquine, or the serine protease inhibitor, tosyl-phenylalanine chloromethyl ketone, reduced the fMLP-stimulated generation of PAF and also reduced the generation of O2-. The respiratory burst induced by a submaximal concentration of phorbol myristate acetate was not affected by these compounds. These data are consistent with the suggestion that endogenous PAF may contribute to the signal transduction cascade initiated by fMLP.