Role of calcium and protein kinase C in platelet activating factor- induced activation of peritoneal macrophages

Abstract

Particulate or soluble stimuli appear to stimulate phagocytic cell's response by the change of Ca2+ mobilization and by the activation of protein kinase C. In contrast, it is reported that activation of protein kinase C could attenuate agonist-stimulated elevation of Ca2+i in neutrophils. PAF elicited an increase of Ca2+i in peritoneal macrophages in a dose dependent fashion and Ca2+ extrusion was accompanied. PAF-induced elevation of Ca2+i was not affected by TMB-8, verapamil and TTX. TEA stimulated PAF-induced mobilization of Ca2+i and delayed lowering of Ca2+i. Five mM EGTA almost completely inhibited PAF-induced mobilization of Ca2+i. After the addition of PAF, membrane permeability was markedly increased up to 5 min and then slowly increased. PAF-induced LDH release was slightly decreased by EGTA plus TMB-8. PAF-stimulated superoxide generation was inhibited by EGTA, TMB-8 and verapamil but not affected by TTX and TEA. PAF-induced elevation of Ca2+i, increased membrane permeability and superoxide generation were inhibited by IQSP, chlorpromazine and propranolol. PAF-induced LDH release was significantly inhibited by chlorpromazine and minimally decreased by propranolol. After the pretreatment with PMA, the stimulatory effect of PAF on the elevation of Ca2+i and LDH release in macrophages was significantly decreased. These results suggest that PAF may exert the stimulatory action on peritoneal macrophages of mouse by the elevation of Ca2+i and by the activation of protein kinase C. Preactivation of protein kinase C appears to attenuate the stimulatory action of PAF on macrophage response.