Human monocyte killing of Staphylococcus aureus: modulation by agonists of cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate

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Abstract
Cyclic[c]nucleotides play a role in the regulation of bacterial killing by human monocytes. Agents were tested for their ability to activate monocyte adenylate or guanylate cyclase in cell-free preparations, to increase cAMP or cGMP in intact human monocytes and to modulate monocyte-induced killing of S. aureus in vitro. Prostaglandin[PG]E1 and cholera toxin activated monocyte adenylate cyclase and inhibited monocyte killing of S. aureus. An adenylate cyclase inhibitor, RMI 12330A, reversed the PGE1-mediated inhibition of bacterial killing, implicating cAMP as the intracellular mediator of this inhibition. Monocyte cGMP levels were increased 5- and 17-fold by 5-hydroxytryptamine and N-methyl-N''-nitro-N-nitrosoguanidine, respectively, but neither agent was effective in modulating monocyte bactericidal activity. Modulation of bactericidal activity in human monocytes did not conform to the yin/yang theory of opposing actions by cAMP and cGMP, for although monocyte-mediated killing of S. aureus was inhibited by cAMP agonists, it was not enhanced by cGMP agonists.