THE DEPRESSION OF PHAGOCYTOSIS BY EXOGENOUS CYCLIC NUCLEOTIDES, PROSTAGLANDINS, AND THEOPHYLLINE

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 E₁, E₂, and F_2α (PGE₁, PGE₂, and PGF_2α) were synergistic with that due to theophylline. Inhibition by PGA₁ and PGA₂ was not. At equal concentrations the order of increasing inhibition of phagocytosis (assayed at 10 min) by the prostaglandins was PGE₁ < PGF_2α < PGE₂ < PGA₁ = PGA₂. 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 [1-¹⁴C]glucose to ¹⁴CO₂ that normally accompanies phagocytosis was found to be depressed in the presence of PGE₁ or theophylline, together or individually as expected from the inhibition of phagocytosis. Paradoxically, oxygen consumption although depressed by theophylline or PGE₁ plus theophylline, was stimulated by PGE₁ alone.