The involvement of calcium and protein kinase C in modulating agonist-stimulated chemotaxis of human neutrophils.
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 Ca2 (EGTA added). NiCl2 dose-dependently inhibited FMLP-stimulated chemotaxis in the presence of extracellular Ca2+; the maximum inhibition obtainable with NiCl2 was similar to that with the absence of extracellular Ca2+. These results suggest that FMLP-stimulated chemotaxis is, at least partially, dependent on stimulation of Ca2+ 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.
Merritt
J E
JE
SmithKline Beecham Pharmaceuticals, Welwyn, Herts, U.K.
Greener
M
M
Hallam
T J
TJ
Swayne
G T
GT
D002118:Calcium / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D009532:Nickel / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D009240:N-Formylmethionine Leucyl-Phenylalanine; C022838:nickel chloride; D009532:Nickel; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium