NEUTROPHIL FUNCTION AFTER EXPOSURE TO POLYCHLORINATED-BIPHENYLS IN-VITRO

Polychlorinated biphenyls (PCBs) are known to be immunotoxic, yet the effects on neutrophil (PMN) function arc not well characterized. We incubated PMNs isolated from rat peritoneum with a mixture of PCB congeners, Aroclor 1242, in the absence or presence of either phorbol myristate acetate (PMA) to stimulate generation of superoxide anion (O2-) or N-formyl-methionylleucyl-phenylalanine (fMLP) to induce degranulation (measured as release of beta-glucuronidase). Arodor 1242 alone stimulated O2 production at a concentration of 10 mug/ml. Significant cytotoxicity was not observed under these conditions. This concentration of Aroclor 1242 also increased O2 generation in PMNs activated with 20 ng PMA/ml. In the presence of a concentration of PMA (2 ng/ml) that by itself did not stimulate production of O2-, 1 mug Aroclor 1242/ml caused significant generation of O2-, indicating synergy between Aroclor 1242 and PMA. Aroclor 1242 caused release of beta-glucuronidase from quiescent PMNs; however, in PMNs stimulated with fMLP to undergo degranulation, Aroclor 1242 inhibited release of beta-glucuronidase. The effects of two PCB congeners, one that binds to the Ah receptor (3,3',4,4'-tetrachlorobiphenyl) and one that has little affinity for this receptor (2,2',4,4'-tetrachlorobiphenyl) were examined. 3,3',4,4'-Tetrachlorobiphenyl had no effect on PMN function in vitro, whereas 2,2',4,4'-tetrachlorobiphenyl had effects similar to those observed with Aroclor 1242. These results indicate that PCBs affect PMN function in vitro in a complex manner, stimulating or inhibiting function under different conditions. These effects are apparently not mediated through the Ah receptor.