Cyclic nucleotide changes in human neutrophils: induced by chemoattractants and chemotactic modulators;
Two classes of agents have effects on the chemotactic response of human neutrophils. Chemoattractants, such as E. coli bacterial factor (BF) and the recently discovered N-formylmethionyl peptides, initiate directed cellular movement, while chemotactic modulators enhance or depress cell movement initiated by chemoattractans. We have previously shown that cyclic adenosine 3’,5’-monophosphate (cAMP) depresses neutrophil migration toward E. coli BF, while cyclic guanosine 3’,5’-monophosphate (cGMP) enhances the same process. In the present study, we examined the effects of chemoattractants and modulators on neutrophil levels of cGMP and cAMP. A simplified radioimmunoassay procedure was developed which employed a rapid heat inactivation of cellular samples rather than the traditional acid inactivation. Three chemoattractants and six chemotactic modulators were tested in concentrations which initiate or modulate cell movement. The chemoattractants, BF, N-formylmethionylalanine, and trypsinized human complement, stimulated the accumulation of neutrophil cGMP (40-70% average increase) but had little effect on cAMP concentrations. The enhancing chemotactic modulators, phenylephrine, prostaglandin F1-alpha, carbachol, and phorbol myristate acetate, also caused significant (p ? 0.05) increases (19-34%) in neutrophil cGMP levels without affecting cAMP concentrations. In contrast, two agents which inhibit the chemotactic response; isoproterenol and prostaglandin E1, significantly elevated cAMP concentrations in these cells. These results suggest that the ability to elevate cGMP is inherent in the action of both chemoattractants and enhancing chemotactic modulators. Increases in cAMP appear to be correlated with inhibition of chemotaxis.
Digital reproduction of “Cyclic nucleotide changes in human neutrophils: induced by chemoattractants and chemotactic modulators.” Spencer S. Eccles Health Sciences Library. Print version of “Cyclic nucleotide changes in human neutrophils: induced by chemoattractants and chemotactic modulators.” available at J. Willard Marriott Library Special Collection. QD 3.5 1977 H38.