The effect of platelet activating factor (PAF), a phagocyte derived mediator, on cytochrome-P-450 dependent metabolism was studied in alveolar type-II cells. Male Sprague-Dawley-rats were injected intraperitoneally with one dose of beta-naphthoflavone (BNF) in corn- oil at 80mg/kg. The lungs were excised 48 hours later, and alveolar type-II cells were isolated. Whole cell and sonicated preparations were assayed for enzyme activity. The findings of this study indicated enhancement of P-450 activity specifically associated with BNF induction and alpha-naphthoflavone sensitivity. The lyso and enantio PAF analogs exhibited actions similar to those observed with PAF. PAF induced enhancement of ethoxyphenoxazone-deethylase activity needed intact cells to be present, while at high PAF concentrations decreased enzyme activity was noted in both intact cell and sonicated cell preparations. The enhancement probably operated at the membrane level within a narrow PAF concentration range and the authors suggest it may reflect specific membrane localization or masked enzyme sites. The authors suggest that xenobiotic metabolism in alveolar type-II cells may be modified by an inflammatory mediator produced by alveolar phagocytes.
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