Exposure to high concentrations of
oxygen is known to induce changes in lung function through effects on several pulmonary cell types, including alveolar macrophages (AM). In this study, we studied the in vitro effects of
hyperoxia on the release of proinflammatory
cytokines and the expression of surface receptors in AM obtained from cynomolgus monkeys by bronchoalveolar lavage under
general anesthesia. AM were exposed for 24 h to moderate (50% O(2)) or severe (95% O&sub2)
hyperoxia in the absence or presence of LPS, and the release of IL-1beta,
IL-6, and
TNF-alpha was measured in culture supernatants by ELISA. In addition, the expression of the surface molecules
HLA-DR, CD14, and CD11b was assessed by flow cytometry. Exposure to 95% O2 activated resting AM to produce significantly increased amounts of IL-1beta and
IL-6. Moreover,
hyperoxia amplified the release of
TNF-alpha by LPS-stimulated AM in an
oxygen tension-dependent manner. Finally, exposure to 95% O2 upregulated the expression of the adhesion molecule CD11b on AM, whereas the expression of
HLA-DR and CD14 was not affected. These findings support the view that
hyperoxia-induced activation of AM may represent an initial event in the proinflammatory sequence caused by
hyperoxia.