Effect of three polychlorinated biphenyls on f-met-leu-phe-induced degranulation in rat neutrophils.
It has been known that polychlorinated biphenyl (PCB) mixtures and individual congeners produce degranulation of rat neutrophils. Structure-activity relationships for congeners PCB 8 (2,4'-dichlorobiphenyl), PCB 126 (3,3',4,4',5-pentachlorobiphenyl) and PCB 128 (2,2',3,3',4,4'-hexachlorobiphenyl) were examined by correlating the extent of degranulation and cytotoxicity with molecular and physico-chemical parameters. Neutrophils were exposed to PCB congeners and then to the neutrophil activator f-met-leu-phe (fmlp). Degranulation and cytotoxicity were quantified by measuring released myeloperoxidase and lactate dehydrogenase activities, respectively. Degranulation in the absence of fmlp, that is in quiescent neutrophils, was detected only for PCB 8. Inhibition of fmlp-induced degranulation was observed for both PCB 8 (50 microM) and PCB 128 (10 and 50 microM). PCB 126 did not affect degranulation of quiescent or fmlp-stimulated neutrophils. Thus, effects on degranulation were observed only for ortho-substituted congeners. Cytotoxicity was observed under all conditions with PCB 8, in quiescent neutrophils with PCB 128, and in activated neutrophils with PCB 126. Structure-activity relationships revealed that effects of PCBs on neutrophil degranulation correlate with the energy of the lowest unoccupied molecular orbital but not with torsional angle 2,1,1',2'. This study demonstrates the importance of molecular, electronic parameters in PCB-induced effects on neutrophil degranulation.
Olivero-Verbel
J
J
Department of Pharmacology and Toxicology, Institute for Environmental Toxicology, Michigan State University, East Lansing 48824, USA.
Ganey
P E
PE
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects*; D003594:Cytoplasmic Granules / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D009240:N-Formylmethionine Leucyl-Phenylalanine; D011078:Polychlorinated Biphenyls; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; C014218:2,3,4,2',3',4'-hexachlorobiphenyl; C023035:3,4,5,3',4'-pentachlorobiphenyl; C029907:2,4'-dichlorobiphenyl