Inhibitory action of elevated levels of adenosine-3':5' cyclic monophosphate on phagocytosis: effects on macrophage-Trypanosoma cruzi interaction.

The effects of agents that elevate intracellular levels of cyclic AMP on the in vitro interaction of mouse peritoneal macrophages with virulent bloodstream forms of a reticulotropic strain of Trypanosoma cruzi were investigated as a part of our efforts to define the requirements for tissue invasion by this intracellular human pathogen. At optimal, non-toxic concentrations, both L-isoproterenol and prostaglandin E1, agents that increase cyclic AMP levels by activating adenylate cyclase via different mechanisms, reduced the uptake by T. cruzi by the macrophages by approximately 30 and 70%, respectively, and also caused a reduction in the numbers of macrophages capable of incorporating the parasites. Similar results were obtained when either theophylline, which increases cyclic AMP levels by inhibiting the catabolic effect of phosphodiesterase activity, was incorporated into the cultures or by direct addition of dibutyryl cyclic AMP. Reductions produced with optimal concentrations of these drugs amounted to approximately 40 to 50%. The present results indicate that binding and uptake of virulent forms of a reticulotropic strain of T. cruzi by macrophages from a susceptible host are under the regulatory influence of cellular cyclic AMP levels.