Mediators of immune-complex-induced aggregation of polymorphonuclear neutrophils. II. Platelet-activating factor as the effector substance of immune-induced aggregation.
Platelet-activating factor (PAF) is released in vitro during human and rabbit polymorphonuclear neutrophil (PMN) aggregation induced by C5a anaphylatoxin, neutrophil cationic proteins (CP) and their carboxypeptidase-B-derived fragments, C5a des Arg and CP des Arg, as well as phagocytosis of opsonized baker's yeast particles and immune complexes (IC). Purified PAF itself is able to cause in vitro PMN aggregation. By using selective inhibitors, we show that PMN aggregation, induced either by PAF or by other soluble stimuli such as C5a, CP and their des Arg products, follows a similar metabolic pathway, which is both adenosine-diphosphate-(ADP)- and arachidonic acid (AA)- independent. The in vivo injection of purified PAF into rabbits leads both to formation of intravascular PMN aggregates and to development of acute neutropenia, which has the same features as those observed after challenge with IC, C5a and CP. In this respect, electron-microscopic studies of intravascular PMN aggregates in the pulmonary capillary network and glomeruli show identical ultrastructural patterns. Moreover, the intravascular release of PAF is demonstrated after the intravenous injection of IC and temporally correlated with the development of neutropenia. We suggest that PAF is probably the final, common, effector substance of IC-, C5a-, C5a-des-Arg-, CP-, CP-des-Arg-mediated PMN aggregation.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D000936:Antigen-Antibody Complex; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D002449:Cell Aggregation; D003182:Complement C5; D003571:Cytochalasin B / Q000494:pharmacology; D006801:Humans; D009503:Neutropenia / Q000209:etiology; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis; D011817:Rabbits; D013928:Thromboxane A2 / Q000096:biosynthesis
D000936:Antigen-Antibody Complex; D001095:Arachidonic Acids; D001798:Blood Proteins; D003182:Complement C5; D003571:Cytochalasin B; D013928:Thromboxane A2; D000244:Adenosine Diphosphate