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 micrograms/ml 2,2',4,4'-TCB prior to stimulation with phorbol myristate acetate (PMA), and superoxide anion (O2-) production was measured. 2,2',4,4'-TCB alone elicited O2- production and potentiated the response to PMA. When neutrophils were incubated in calcium-free medium, the ability of TCB to stimulate O2- 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 O2- 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 micrograms/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 O2- 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.
Brown
A P
AP
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824, USA.
Ganey
P E
PE
D000818:Animals; D001202:Ascitic Fluid; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000633:toxicity; D015550:Cell Degranulation / Q000187:drug effects*; D004347:Drug Interactions; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D002121:Calcium Channel Blockers; D013481:Superoxides; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D011078:Polychlorinated Biphenyls; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium