Cigarette smoke-induced alterations in the release of arachidonate metabolites by pulmonary alveolar macrophage from selenium-fed and selenium-deficient rats.
Male weanling F-344 rats were maintained on selenium-supplemented or -deficient diets and were exposed to fresh cigarette smoke daily for 28 weeks. The deficient status of animals was demonstrated by a significant reduction in the pulmonary and hepatic glutathione peroxidase (GSH-Px) activity of rats on selenium-deficient diet. Sham and smoke treatment did not influence the GSH-Px activity in either diet group. Elevated levels of blood carboxyhemoglobin and pulmonary aryl hydrocarbon hydroxylase activity in the smoke-exposed rats of both diet groups indicated effective inhalation of cigarette smoke by animals. Studies of the extracellular release of arachidonate metabolites by pulmonary alveolar macrophages (PAMs) indicated that resting cells released small amounts of prostaglandin E2 (PGE2), thromboxane B2 (TXB2) and leukotriene B4 (LTB4). Upon phagocytic challenge by opsonized zymosan particles, the release of the three metabolites was substantially increased in all diet and treatment groups. While the release of cyclooxygenase products, PGE2 and TXB2, remained unaffected by cigarette smoke, an inhibition of approximately 50% in the release of lipoxygenase product, LTB4, was observed in cells from selenium-fed animals. In selenium-deficient animals, cigarette smoke almost completely inhibited (greater than 80%) the zymosan-stimulated release of LTB4 by PAMs and additionally caused about 50% reduction in TXB2 release. These results suggest a specific inhibition of lipoxygenase pathway by cigarette smoke in PAMs of selenium-fed rats and suggest that cigarette smoke may additionally impair enzymes of the cyclooxygenase pathway in PAMs of selenium-deficient animals.
D000284:Administration, Oral; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001835:Body Weight; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D005979:Glutathione Peroxidase / Q000032:analysis; D007975:Leukotriene B4 / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010587:Phagocytosis; D010947:Plants, Toxic; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D011916:Rats, Inbred F344; D012643:Selenium / Q000008:administration & dosage / Q000172:deficiency* / Q000494:pharmacology; D012906:Smoke; D013929:Thromboxane B2 / Q000378:metabolism; D014026:Nicotiana
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011458:Prostaglandins E; D012906:Smoke; D007975:Leukotriene B4; D016718:Arachidonic Acid; D013929:Thromboxane B2; D005979:Glutathione Peroxidase; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D012643:Selenium; D015232:Dinoprostone