HUMAN ALVEOLAR MACROPHAGE ANTIBACTERIAL ACTIVITY IN THE ALCOHOLIC LUNG

Alcoholic individuals are predisposed to respiratory infections. However mechanisms of perturbations leading to increased susceptibility to lung infections of individuals with alcoholic liver cirrhosis (ALC) are not fully understood. We studied the antibacterial activity and oxidant generation (before and after stimulation by phorbol myristate acetate or opsonized zymosan) of alveolar macrophages from 16 patients with ALC. Our results were compared with those obtained from 12 healthy control subjects, from 8 patients with primary biliary cirrhosis (PBC), and from 8 alcoholic individuals without cirrhosis. All were nonsmokers, had normal chest X-rays, and did not present evidence of lung infection 3 months before. The total number of cells recovered by bronchoalveolar lavage did not significantly differ between control subjects and patients. The cellular viability of alveolar macrophages (trypan blue exclusion) was > 90% in all cases. The antibacterial activity of alveolar macrophages versus Staphylococcus aureus was severely impaired in ALC (-21 +/- 8.2%) whereas it was normal in PBC (52 +/- 4.2%), in alcoholic subjects (44.6 +/- 5.4%), and in control subjects (60 +/- 5.5%). The same pattern of results was observed versus Escherichia coli (-47.7 +/- 10, 28 +/- 8, 28 +/- 12, and 29 +/- 8.5%, respectively). Previous incubation of normal alveolar macrophages with serum or BAL fluid from ALC patients or with normal serum or normal BAL fluid did not result in a significant decrease in antibacterial activity of normal alveolar macrophages. To distinguish ingested bacteria from adherent extracellular bacteria, cells that had been incubated with bacteria for 90 min were then incubated with lysostaphin (1-mu-g/ml). The results clearly demonstrated that an antibacterial defect of alveolar macrophages from ALC patients was largely caused by abnormal bacterial uptake. Adherence of alveolar macrophages from ALC patients and from healthy control subjects was not significantly different. Free-radical generation before and after stimulation by alveolar macrophages from patients with ALC or PBC or alcoholic subjects was not significantly decreased compared with that in control subjects. Surprisingly, alveolar macrophages from patients with ALC or PBC or alcoholic subjects released greater amounts of superoxide anion than alveolar macrophages from control subjects. Our results suggest that impaired antibacterial activity of alveolar macrophages in ALC is not caused by abnormal oxidative metabolism of phagocytes but may be due to a defect in bacterial uptake. Abnormalities of macrophage function may, at least in part, account for an Increased susceptibility of patients with alcoholic cirrhosis to infection.