Participation of Ca2+/calmodulin during activation of rat neutrophils by polychlorinated biphenyls

The effects of Ca2+ and Ca2+/calmodulin on the polychlorinated biphenyl (PC B)-induced activation of phospholipase A(2) (PLA(2)) in rat neutrophils wer e examined. The commercial PCB mixture Aroclor 1242 induced activation of P LA(2) and promoted an increase in the intracellular free calcium concentrat ion ([Ca2+](i)). Bromoenol lactone (BEL), an inhibitor of the Ca2+-independ ent PLA(2) isoform (iPLA(2)) activated by PCBs, did not abrogate the increa se in [Ca2+](i), suggesting that this change in Ca2+ concentration is not d ownstream from the activation of iPLA(2). TMB-8 [8-(N,N-diethylamino)octyl- 3,4,5-trimethoxybenzoate], a blocker of the release of intracellular Ca2+, decreased Aroclor 1242-induced stimulation of PLA(2) with a maximal inhibit ion of 17% at 50 muM. These two results suggest little direct dependence be tween the PCB-induced activation of iPLA(2) and increase in [Ca2+](i). Calm idazolium and W7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], two chemically distinct calmodulin inhibitors, inhibited Aroclor 1242-induced P LA, activity, whereas trifluoperazine (TFP), another inhibitor of calmoduli n, had no effect at noncytotoxic concentrations. Thus, activation of PLA(2) is dependent, in part, on calmodulin. Furthermore, both TFP and Aroclor 12 42 inhibited neutrophil degranulation stimulated by the bacterial peptide f ormylmethionyl-leucyl-phenylalanine. These results raise the possibility th at some of the effects of PCBs on neutrophil function can be explained by e ffects on Ca2+/calmodulin-dependent processes. (C) 2001 Elsevier Science In c. All rights reserved.