EFFECT OF CYCLIC-AMP LEVEL REDUCTION ON HUMAN NEUTROPHIL RESPONSES TOFORMYLATED PEPTIDES

The increase in human neutrophil cyclic adenosine monophosphate (cAMP) levels evoked by formylated peptides is significantly reduced in the presence bf MDL 12330A, Sa 22536, GDP beta S and clonidine, which inhi bit the adenylyl cyclase system by acting at different sites in this e nzyme complex. A similar effect is exerted by adenosine deaminase and dipyridamole, which alter the extracellular adenosine concentration. N eutrophil preincubation with adenylyl cyclase inhibitors or dipyridamo le reduces chemotaxis and superoxide anion production triggered by pep tides; adenosine deaminase, on the contrary, has no effect on neutroph il responses. Our results seem to indicate that: (1) the peptide-induc ed increase in neutrophil cAMP is due mainly to an action on the adeny lyl cyclase system; (2) an enhancement of this cyclic nucleotide, even slight and necessarily transient, is required for chemotaxis and O-2( -) production induced in neutrophils by formylated peptides; and (3) c AMP does not represent the crucial second messenger for adenosine in t he modulation of neutrophil responses.