Ortho substituted polychlorinated biphenyls elevate intracellular [Ca(2+)] in human granulocytes

The perturbation of Ca(2+)-homeostasis in human granulocytes exposed to ortho and non ortho substituted polychlorinated biphenyls (PCB) was investigated. Ortho substituted PCB congeners increased intracellular free calcium, [Ca(2+)]i, in a concentration-dependent manner. The increase in [Ca(2+)]i was inversely proportional to the total surface area of the ortho substituted congeners. The effect of ortho substituted PCB congeners was dependent upon external Ca(2+) and phospholipase C activation, except for a tetra-ortho substituted congener, 2,2',6,6'-TeCB, that was not phospholipase C-dependent. We suppose that PCBs activate phospholipase C which leads to the production of ins(1,4,5)P3. This will release Ca(2+) from intracellular stores and subsequently activation of Ca(2+) release activated Ca(2+) channels (CRAC) in the plasma membrane. It is also possible that PCBs activate CRAC in a more direct manner. Our findings show that ortho substituted PCB congeners stimulate [Ca(2+)]i elevation in human granulocytes, and this could in part account for the effects of PCB on the immune system.