A ROLE FOR CALCIUM AND PROTEIN KINASE-C IN AGONIST-STIMULATED ADHESION OF HUMAN NEUTROPHILS

Stimulated adherence of human neutrophils to plastic and changes in cytosolic free Ca2+ concn. ([Ca2+](i)) were measured in the same cell preparations. [Ca2+](i)-activation curves were constructed to compare the relation between [Ca2+](i) and adhesion in response to ionomycin and formylmethionyl-leucyl-phenylalanine (FMLP). This showed that FMLP-stimulated adhesion required less increase in [Ca2+](i) than did ionomycin's effect, a result suggesting that an additional stimulatory component might be involved in the response to FMLP. Protein kinase C activation was a possibility, and activation of protein kinase C with a phorbol ester (PMA) was found to stimulate adhesion with no change in [Ca2+](i). A low concentration of PMA was found to synergize with ionomycin to stimulate a greater adhesion response than with each alone, and the [Ca2+](i)-activation curve for ionomycin in the presence of PMA was shifted towards that for FMLP. Thus, synergy between [Ca2+](i) and protein kinase C (each of which is sufficient alone) probably explains the stimulatory effects of FMLP on adhesion of neutrophils.