ORTHO-SUBSTITUTED POLYCHLORINATED-BIPHENYLS ELEVATE INTRACELLULAR [CA2+] IN HUMAN GRANULOCYTES

The perturbation of Ca2+-homeostasis in human granulocytes exposed to ortho and non ortho substituted polychlorinated biphenyls (PCB) was in vestigated. Ortho substituted PCB congeners increased intracellular fr ee calcium, [Ca2+](i), in a concentration-dependent manner. The increa se in [Ca2+](i) was inversely proportional to the total surface area o f the ortho substituted congeners. The effect of ortho substituted PCB congeners was dependent upon external Ca2+ and phospholipase C activa tion, except for a tetra-ortho substituted congener, 2,2',6,6'-TeCB, t hat was not phospholipase C-dependent. We suppose that PCBs activate p hospholipase C which leads to the production of ins(1,4,5)P3. This wil l release Ca2+ from intracellular stores and subsequently activation o f Ca2+ release activated Ca2+ channels (CRAC)in the plasma membrane. I t is also possible that PCBs activate CRAC in a more direct manner. Ou r findings show that oi tho substituted PCB congeners stimulate [Ca2+] (i) elevation in human granulocytes, and this could in part account fo r the effects of PCB on the immune system. (C) 1998 Elsevier Science B .V. All rights reserved.