Multiple defects in arachidonate metabolism in alveolar macrophages from young asymptomatic smokers.
This study was undertaken to localize and determine the relative importance of potential biochemical defects in the release and metabolism of arachidonic acid (AA) in alveolar macrophages (AMs) from asymptomatic smokers. Using high-performance liquid chromatography and radioimmunoassay, we compared the metabolism of both endogenously released and exogenously supplied AA in AMs and autologous peripheral blood monocytes (PBMs) from nine healthy nonsmokers and eight healthy smokers. AMs from both groups incorporated similar amounts of radiolabeled AA into cellular lipids. However, AMs from smokers released only about half as much radioactivity as free AA and its metabolites in response to ionophore A23187, when compared to cells from nonsmokers; this suggests that net phospholipase activity was decreased in smokers. In addition, AMs from smokers synthesized less of total cyclooxygenase and 5-lipoxygenase products than did cells from nonsmokers, both constitutively and in response to A23187 as well as the particulate agonist zymosan. Furthermore the metabolism of exogenous AA to both cyclooxygenase and 5-lipoxygenase products was reduced in smoker cells compared to nonsmoker cells. Inverse relationships between eicosanoid synthesis and intensity of smoking were observed. No differences between smoker and nonsmoker PBMs were found. These results show that the major defect in smoker AMs is at the phospholipase level, with additional defects being present at the levels of the cyclooxygenase and 5-lipoxygenase pathways. All these abnormalities are compartmentalized to the mononuclear phagocyte population of the lung.
Balter
M S
MS
Pulmonary Division, University of Michigan, Ann Arbor.
Toews
G B
GB
Peters-Golden
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D015777:Eicosanoids / Q000096:biosynthesis; D008055:Lipids / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism; D011863:Radioimmunoassay; D012907:Smoking / Q000378:metabolism*; D015054:Zymosan / Q000494:pharmacology
D000975:Antioxidants; D001095:Arachidonic Acids; D015777:Eicosanoids; D008055:Lipids; D016718:Arachidonic Acid; D000001:Calcimycin; D000255:Adenosine Triphosphate; D015054:Zymosan; D010105:Oxygenases; D010740:Phospholipases