NEUTROPHIL DEGRANULATION AND SUPEROXIDE PRODUCTION INDUCED BY POLYCHLORINATED-BIPHENYLS ARE CALCIUM-DEPENDENT

2,2',4,4'-Tetrachlorobiphenyl (TCB), a polychlorinated biphenyl (PCB), alters neutrophil functions in vitro by unknown mechanisms. The role of calcium in mediating PCB stimulation of neutrophil function was investigated. Peritoneal neutrophils were isolated from retired breeder, male, Sprague-Dawley rats. Neutrophils were incubated with 10 mu g/ml 2,2',4,4'-TCB prior to stimulation with phorbol myristate acetate (PMA), and superoxide anion (O-2(-)) production was measured. 2,2',4,4'-TCB alone elicited OS production and potentiated the response to PMA. When neutrophils were incubated in calcium-free medium, the ability of TCB to stimulate O-2(-) production and to potentiate the response to PMA was abolished. The absence of extracellular calcium did not alter the response to PMA alone. TMB-8, an antagonist of the mobilization of intracellular calcium, inhibited O-2(-) production in response to 2,2',4,4'-TCB stimulation but not to PMA. Degranulation of neutrophils, measured by release of myeloperoxidase, occurred upon exposure to 10 mu g/ml 2,2',4,4'-TCB alone. This response was increased by cotreatment with the calcium ionophore A23187. 2,3,4,5-TCB, a mono-ortho-substituted PCB congener, potentiated O-2(-) production in response to PMA stimulation by a mechanism that was partly dependent on the presence of extracellular calcium. This congener also stimulated neutrophils to release myeloperoxidase. 3,3',4,4'-TCB, a coplanar congener with high affinity for the Ah receptor, did not elicit neutrophil degranulation. These results indicate that TCBs affect neutrophil function in vitro through signal transduction pathways that appear to be calcium dependent. (C) 1995 Academic Press,Inc.