The effects of clofibrate ingestion on alveolar macrophage peroxisome content and oxygen metabolism.
Respiratory burst activity in alveolar macrophages in response to particulate and soluble challenges, such as zymosan particles and phorbol myristate acetate (PMA), is not nearly as dependent upon membrane stimulation as in neutrophils. Microperoxisomes are subcellular organelles containing catalase and are present in lung macrophages and cells of other organs. Evidence from liver cells indicates that peroxisomes are intimately involved with hydrogen peroxide and lipid metabolism. Clofibrate (2-(p-chlorophenoxy)-2-methylpropionic acid ethyl, Atromid-S-), a hypolipidemic drug known to cause peroxisomal proliferation in liver cells, was studied with respect to its ability to cause increases in the microperoxisome content and to alter the cellular metabolism of alveolar macrophages. Liver weight increased over a 2-week drug treatment period while lung weight remained unchanged. Plasma triglyceride levels were decreased by the treatment, indicating the effectiveness of the drug. Unlike the effect on liver cells, however, clofibrate did not cause a proliferation of microperoxisomes, as determined by morphometric analysis. Oxygen consumption and hydrogen peroxide generation by alveolar macrophages in response to either stimulant (zymosan or PMA) was no greater in clofibrate-treated rats than in controls. Superoxide release, when expressed as the change in response to PMA, appeared elevated in the drug group; statistical significance, however, was not demonstrated. The hexose monophosphate shunt (HMP), which produces reducing equivalents for lipid biosynthesis, was elevated in macrophages from clofibrate-treated rats when expressed similarly. The significance of these results in relation to the known effects of the drug on liver cells.
D000818:Animals; D002994:Clofibrate / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000378:metabolism; D009940:Organoids / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D006861:Hydrogen Peroxide; D002994:Clofibrate