Mechanisms of ethanol-induced defects of alveolar macrophage function.

Several defects in host defense mechanisms of alcoholics have been described, but their role in the development of infections, especially pneumonia, is uncertain. Ethanol, in concentrations of 400 mg/100 ml, inhibits phagocytosis of radiolabeled bacteria by rabbit alveolar macrophages from 73 to 80% of control. Intracellular survival of Staphylococcus aureus is increased to 131% of control by exposure to ethanol. To evaluate the mechanisms of these ethanol-induced defects, the effect of ethanol on microtubular function and changes in levels of cAMP were evaluated. Colchicine (10(-6) M), a disrupter of microtubules, produces 49% capped cells (migration of fluorescein isothiocyanate-labeled concanavalin A (FITC-ConA) to one end of the cell), but ethanol produces no capping, even at concentrations of 2000 mg/100 ml. This suggests that the ethanol effect is not mediated by disruption of microtubules. cAMP levels, measured by radioimmunoassay, increased two-fold over control values after 10 min incubation with ethanol. The increase is dose dependent with a rapid onset. The effect of ethanol on alveolar macrophages is probably complex, but changes in osmolarity and increases in cAMP levels, perhaps interrelated by some pertubation in the cell membrane, may explain the defect.