Decreased Bactericidal Function and Impaired Respiratory Burst in Lung Macrophages after Sustained in vitro Hyperoxia

Abstract

Lung macrophages (LM) play a crucial role in pulmonary bacterial defense. High inspired oxygen concentrations are used in a variety of diseases and "oxygen toxicity" could impair antibacterial function. We therefore examined the effect of sustained in vitro hyperoxia on LM bactericidal function, and on generation of two bactericidal oxygen metabolites. The LM were cultivated under aerobic (PO2 approximately 140 mmHg) or hyperoxic (PO2 approximately 630 mmHg) conditions for 48 h, and then incubated with Staphylococcus aureus labeled with 3H thymidine for 30 min. Incubated monolayers were processed for measurement of total bacterial uptake and for number of viable intracellular bacteria. Superoxide anion (O2-) and hydrogen peroxide (H2O2) generation was determined in similarly cultivated cells stimulated with opsonized zymosan. The results indicate that the bacterial killing capacity of oxygen-cultivated LM is significantly decreased (p less than 0.001). In addition, a significant (p less than 0.001) decrease in generation of O2- and H2O2 was noted after exposure to high oxygen tensions. The data suggest that decreased bactericidal function after sustained hyperoxia may be due to an impairment of a specific bactericidal mechanism, i.e., an impaired "respiratory burst."