The depression of phagocytosis by exogenous cyclic nucleotides, prostaglandins, and theophylline

Abstract

The effects of agents that elevate intracellular cyclic adenosine 3',5'-monophosphate (cAMP) have been studied with respect to phagocytosis by guinea pig polymorphonuclear leukocytes. The investigation depends upon the use of a precise method for following ingestion. Theophylline, dibutyryl cAMP, and prostaglandins inhibited the phagocytosis of starch particles. The inhibitions caused by prostaglandins E(1), E(2), and F(2alpha) (PGE(1), PGE(2), and PGF(2alpha)) were synergistic with that due to theophylline. Inhibition by PGA(1) and PGA(2) was not. At equal concentrations the order of increasing inhibition of phagocytosis (assayed at 10 min) by the prostaglandins was PGE(1) < PGF(2alpha) < PGE(2) < PGA(1) = PGA(2). Our results are consistent with the hypothesis that increased intracellular levels of cAMP impair the phagocyte's ability to ingest particles. The mechanism of the inhibition has not been defined. The increment in oxidation of [1-(14)C]glucose to (14)CO(2) that normally accompanies phagocytosis was found to be depressed in the presence of PGE(1) or theophylline, together or individually as expected from the inhibition of phagocytosis. Paradoxically, oxygen consumption although depressed by theophylline or PGE(1) plus theophylline, was stimulated by PGE(1) alone.