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 in cubated PMNs isolated from rat peritoneum with a mixture of PCB congen ers, Aroclor 1242, in the absence or presence of either phorbol myrist ate 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 stimul ated O2 production at a concentration of 10 mug/ml. Significant cytoto xicity 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 i tself did not stimulate production of O2-, 1 mug Aroclor 1242/ml cause d significant generation of O2-, indicating synergy between Aroclor 12 42 and PMA. Aroclor 1242 caused release of beta-glucuronidase from qui escent PMNs; however, in PMNs stimulated with fMLP to undergo degranul ation, Aroclor 1242 inhibited release of beta-glucuronidase. The effec ts of two PCB congeners, one that binds to the Ah receptor (3,3',4,4'- tetrachlorobiphenyl) and one that has little affinity for this recepto r (2,2',4,4'-tetrachlorobiphenyl) were examined. 3,3',4,4'-Tetrachloro biphenyl had no effect on PMN function in vitro, whereas 2,2',4,4'-tet rachlorobiphenyl had effects similar to those observed with Aroclor 12 42. These results indicate that PCBs affect PMN function in vitro in a complex manner, stimulating or inhibiting function under different co nditions. These effects are apparently not mediated through the Ah rec eptor.