Human Alveolar Macrophage Antibacterial Activity in the Alcoholic Lung

Abstract

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 greater than 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 microgram/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of alveolar macrophages from pulmonary patients and healthy subjects with liposomes

“…These data are consistent with the f'mding [8] that PM has a greater effect on the formation of superoxide radical in AM from patients with cirrhosis of the liver in comparison with healthy subjects. In our experiments activation of oxidative burst was noted only in AM from patients with chronic bronchitis.…”

“…Interaction of liposomes of various composition with transformed macrophage strains [4], bone marrow [3], and animal alveolar macrophages [7] is now intensely investigated. However, the information on interactions with cells of the human mononuclear phagocyte system is scarce [8].…”

Risk factors for mortality in cirrhotic patients with sepsis

“…Abnormal respiratory cellular function in cirrhosis might contribute to this phenomenon, as pulmonary clearance of organisms was markedly reduced in cirrhotic rats and was associated with reduced serum complement levels [13]. The impaired phagocytic activity [14] and cytokine production by alveolar macrophages [15] in patients with cirrhosis might explain their poor response to lung infections. In a surveillance study of persons who were hospitalized for pneumonia secondary to Streptococcus pneumoniae infection in 1995-1997, increased mortality was associated with underlying disease, such as liver cirrhosis, and cancer [16].…”

Infections in Liver Disease

“…In the presence of widespread immune dysfunction, these factors contribute to higher incidence of adult respiratory distress syndrome (ARDS) in cirrhosis. 40,41 Patients with cirrhosis and sepsis are more likely to die with ARDS compared to individuals with ARDS who did not have cirrhosis. Patients with cirrhosis requiring mechanical ventilation have mortality rates well above 50% and as high as 100% in one series.…”