AGENTS THAT ELEVATE CAMP INHIBIT HUMAN NEUTROPHIL APOPTOSIS

Neutrophil apoptosis, determined after 20 h in culture using standard criteria and shedding of cell surface CD16 (Fc gamma RIII), is dramati cally inhibited, in a concentration-dependent manner, by the cAMP anal ogs, dibutyryl-cAMP and 8-Br-cAMP, and the adenylyl cyclase activator, forskolin. Furthermore, the stable receptor-directed PGD(2) mimetic, ZK 118,182, and the PGE(2) mimetic, Il-deoxy PGE(1), similarly inhibit ed apoptosis. The DP-receptor antagonist BW A868C blocked the effect o f ZK 118,182 and the protein kinase A inhibitor H-89 reversed the inhi bition of apoptosis induced by dibutyryl-cAMP. These results clearly s how that neutrophil apoptosis is markedly attenuated by cAMP elevating agents. This nucleotide second messenger may play a fundamental role in controlling neutrophil longevity and pharmacological regulation of cAMP levels or actions may influence neutrophil apoptosis in vivo. (C) 1995 Academic Press. Inc.