title: Neutrophil function after exposure to polychlorinated biphenyls in vitro.
abstract: Polychlorinated biphenyls (PCBs) are known to be immunotoxic, yet the effects on neutrophil (PMN) function are 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-methionyl-leucyl-phenylalanine (fMLP) to induce degranulation (measured as release of beta-glucuronidase). Aroclor 1242 alone stimulated O2- production at a concentration of 10 micrograms/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 microgram 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.
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
authors.forename: P E
authors.initials: PE
authors.lastname: Ganey
authors.forename: J E
authors.initials: JE
authors.lastname: Sirois
authors.forename: M
authors.initials: M
authors.lastname: Denison
authors.forename: J P
authors.initials: JP
authors.lastname: Robinson
authors.forename: R A
authors.initials: RA
authors.lastname: Roth
mesh_terms: D000818:Animals; D005966:Glucuronidase / Q000097:blood / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D013481:Superoxides; C035976:2,4,2',4'-tetrachlorobiphenyl; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011078:Polychlorinated Biphenyls; D005966:Glucuronidase; D013755:Tetradecanoylphorbol Acetate; C028451:3,4,3',4'-tetrachlorobiphenyl