Bidirectional Regulation of Lysosomal Enzyme Secretion and Phagocytosis in Human Neutrophils by Guanosine 3′,5′-Monophosphate and Adenosine 3′,5′-Monophosphate 1

Abstract

Summary

The biologic roles of guanosine 3′,5′-monophosphate (cyclic GMP) and adenosine 3′,5′-monophosphate (cyclic AMP) in the secretion of lysosomal enzymes from, and in phagocytosis by, human neu-trophils were studied. Contact between neutrophils and particulate immunologic reactants results in both phagocytosis of the particles and secretion of lysosomal enzymes. These cellular events are accompanied by the accumulation of cyclic GMP and require the presence of extracellular calcium. Acetylcholine, pilocarpine, and cyclic GMP enhance, whereas epinephrine, cyclic AMP, and/or dibutyryl cyclic AMP inhibit, both phagocytosis and lysosomal enzyme secretion. The stimulatory action of cholinergic agents and the inhibitory action of epinephrine are accompanied by the accumulation of cyclic GMP and cyclic AMP, respectively, in human neutrophils. The data suggest that cyclic GMP mediates whereas cyclic AMP inhibits the major functions of human neutrophils. Moreover, by virtue of their effects on cyclic nucleotide accumulation, autonomic neurohormones are capable of modulating human neutrophil function.