Superoxide anion release induced by platelet-activating factor is increased in human alveolar macrophages from smokers

This study was designed to investigate the effects of the platelet-activating factor (PAF) on the superoxide anion production (O2.) of human alveolar macrophages (AM) from nonsmoking (n = 18) and smoking (n = 30) subjects. Freshly isolated cells were stimulated with (PAF) or with a phorbol ester (phorbol 12-myristate 13 acetate (PMA)). Stimulation with PAF led to a dose-dependent increase of O2. production by AM in both groups. The median effective dose (EC50) for PAF action on O2. production of smoker AM was 0.5 x 10(-8) M, compared to nonsmoker AM with an EC50 of 1.0 x 10(-7) M. This effect of PAF was blockable by the PAF-antagonist WEB 2086 in a dose-dependent manner. Comparison of the relative increase of O2. production after PAF-stimulation showed that smoker cells were significantly more sensitive to PAF than nonsmoker cells (p less than 0.01). In contrast to the findings with PAF, the relative increase of O2. production after PMA-stimulation showed no differences between smoker and nonsmoker AM. Our data suggest that AM from smoking subjects are more sensitive to PAF than AM from nonsmokers.