Enhanced chemotaxis and superoxide anion production by polymorphonuclear leukocytes from nicotine-treated and smoke-exposed rats.
Although previous studies have shown that polymorphonuclear leukocytes (PMNs) exposed to nicotine in vitro exhibit enhanced superoxide anion generation and chemotactic responses, it is not known whether in vivo exposure to the alkaloid causes the same alterations in PMN function. Accordingly, this study evaluated superoxide anion generation evoked by phorbol myristate acetate (PMA) and chemotactic responses to formylmethionylleucylphenylalanine (fMLP) in PMNs isolated from rats treated acutely or subchronically with nicotine and from rats chronically exposed to cigarette smoke. Acute or subchronic (twice daily for 7 days) i.p. injection of 0.2 or 0.02 mg/kg nicotine potentiated PMA-induced superoxide anion generation by PMNs. Similarly, acute i.p. injection of 0.2 mg/kg nicotine or subchronic treatment with 0.02 mg/kg nicotine potentiated fMLP-induced chemotaxis. Subchronic treatment with 0.2 mg/kg of the alkaloid blunted fMLP-induced chemotaxis, in contrast to the potentiating actions of the lower dose. Treatment with nicotine mimicked the effects of tobacco smoke exposure. A 15-week exposure regimen to either sidestream and mainstream smoke from University of Kentucky 2R1 reference cigarettes potentiated PMA-induced superoxide anion generation. Mainstream but not sidestream smoke also enhanced chemotactic responses to fMLP. Viewed collectively, these observations indicate that in vivo exposure to nicotine or to tobacco smoke augment PMN superoxide anion generation and chemotactic responses to selected stimuli and thus implicate such adverse actions of smoking on PMN function in certain pathologies associated with excessive tobacco smoke exposure.
D000818:Animals; D002470:Cell Survival; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004357:Drug Synergism; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012907:Smoking; D013481:Superoxides / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009538:Nicotine; D013755:Tetradecanoylphorbol Acetate