Recent studies have shown that alveolar macrophages (AM) are able to release leukotrienes (LTs). Since cigarette smoking inhibits the cyclooxygenase pathway of arachidonic acid metabolism in the AM, we evaluated the LT production by AM from smokers and nonsmokers. AM were obtained from 35 volunteers, 16 nonsmokers, and 19 smokers. The cells were incubated under various conditions including stimulation with 30 microM arachidonic acid, 2 microM ionophore A23187, or both. Each experiment was performed in parallel using cells from a smoker and a nonsmoker. Lipoxygenase products were analyzed by reverse-phase high performance liquid chromatography. After stimulation, nonsmokers' AM produced LTB4 and 5-hydroxy-eicosatetraenoic acid (5-HETE). In incubations of AM with arachidonic acid and ionophore, the amounts of products formed were: LTB4, 317 +/- 56 pmol/10(6) cells and 5-HETE, 1,079 +/- 254, mean +/- SEM. No metabolites were generated under control conditions (no stimulation). In all incubations performed, the peptido-LTs (LTC4, LTD4, and LTE4) were undetectable. In comparison with AM from nonsmokers, those from smokers showed a 80-90% reduction of 5-HETE and LTB4 synthesis (P less than 0.05 to P less than 0.001 according to stimulatory conditions). This defective lipoxygenase metabolite production in AM from smokers was observed over a wide range of stimuli concentrations and incubation times; AM from smokers also had lower levels of intracellular (esterified) 5-HETE than nonsmokers' AM. We also studied blood polymorphonuclear leukocytes (PMNL) and no difference in the synthesis of 5-lipoxygenase products in these cells was noticed between smokers and nonsmokers. These data show that cigarette smoking causes a profound inhibition of the 5-lipoxygenase pathway in AM but not in blood PMNL.
M Laviolette, R Coulombe, S Picard, P Braquet, P Borgeat
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Pediatrics International | 1991 |
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New England Journal of Medicine | 1990 |
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1990 | |
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Journal of Allergy and Clinical Immunology | 1989 |
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Immunology | 1988 |
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Journal of Chromatography B: Biomedical Sciences and Applications | 1988 |
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American journal of respiratory and critical care medicine | 1988 |
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GP Brown, MM Monick, GW Hunninghake |
American journal of physiology. Cell physiology | 1988 |
Selective inhibition of 5-lipoxygenase pathway in rat pulmonary alveolar macrophages by cigarette smoking
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American journal of respiratory and critical care medicine | 1987 |
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PR Bachwich, JP Lynch, SL Kunkel |
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Leukotrienes and Airway Responses
JM Drazen, KF Austen |
American journal of respiratory and critical care medicine | 1987 |
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Immune and inflammatory function in cigarette smokers
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Thorax | 1987 |
Cigarette Smoking and Respiratory Tract Infection
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Adult Respiratory Distress Syndrome
JE Rinaldo, RM Rogers |
New England Journal of Medicine | 1986 |