Effect of adenylate cyclase activators on C5a-induced human neutrophil aggregation, enzyme release and superoxide production.

The effect of adenylate cyclase activators on C5a- and f-Met-Leu-Phe-induced human neutrophil aggregation, enzyme release and superoxide production was investigated. C5a-stimulated superoxide production was markedly inhibited by adenylate cyclase activators, and the order of potency was PGE1 greater than isoproterenol greater than epinephrine greater than PGF2 alpha, which correlated with intracellular cAMP levels. However, neutrophil aggregation was inhibited by PGE1, PGE2, isoproterenol and epinephrine only at concentrations greater than 10(-6) M. Lysozyme release was inhibited only via PGEs in the presence of the phosphodiesterase inhibitor, methylisobutylxanthine. These results suggest that in the human neutrophil: (1) C5a-induced superoxide production is more sensitive to regulation by cAMP than neutrophil aggregation or enzyme release, and (2) the type of receptor occupied as well as the threshold level of cAMP are important in the regulation of neutrophil aggregation and enzyme release stimulated by C5a.