The involvement of calcium and protein kinase C in modulating agonist-stimulated chemotaxis of human neutrophils

Abstract

Chemotaxis of human neutrophils in response to a gradient of the chemotactic peptide, fmet-leu-phe (FMLP), was measured by the under-agarose technique. The dose-response curve for FMLP was biphasic; low concentrations were stimulatory, and the response was reduced at higher concentrations. The response to FMLP was partially inhibited (about 50%) in the absence of extracellular Ca 2 (EGTA added). NiCl 2 dose-dependently inhibited FMLP-stimulated chemotaxis in the presence of extracellular Ca 2+; the maximum inhibition obtainable with NiCl 2 was similar to that with the absence of extracellular Ca 2+. These results suggest that FMLP-stimulated chemotaxis is, at least partially, dependent on stimulation of Ca 2+ influx. The phorbol ester, PMA, dose-dependently inhibited chemotaxis; the response was almost completely inhibited by 10 nM PMA. This result indicates that activation of protein kinase C inhibits chemotaxis. These results are discussed in relation to the physiological responses of neutrophils.