The interactive effects of fluoride and N-formyl-L-methionyl-L-leucyl-L-phenylalanine on superoxide production and cAMP levels in human neutrophils

Abstract

The kinetics of superoxide (O₂⁻) production and intracellular cAMP levels were monitored in human neutrophils incubated in vitro with sodium fluoride and the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). F⁻ activation of both the O₂⁻-generating system, NAD(P)H oxidase, and adenylate cyclase was characterized by a prolonged lag period of 8 to 10 min at 37 °C. Adenylate cyclase agonists or cAMP analogues which inhibited FMLP-induced O₂⁻ bursts did not affect O₂⁻ production of F⁻-activated cells. Prior treatment of cells with F⁻ suppressed the short rapid burst elicited by FMLP but not the binding of the tripeptide. FMLP reciprocally decreased the lag period of the F⁻-induced burst by 40 to 50% and, in the case of cells incubated at temperatures below 37 °C, increased the rate of O₂⁻ production. A similar potentiating effect of FMLP on F⁻-induced elevation of intracellular cAMP levels was observed.