title: Hyperoxia induces upregulation of CD11b and amplifies LPS-induced TNF-alpha release by alveolar macrophages.
abstract: 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.
authors.affiliation: Institute for Surgical Research, University of Munich, Marchioninistr. 15, Munich, D-81377, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Burges
authors.forename: A
authors.initials: A
authors.lastname: Allmeling
authors.forename: F
authors.initials: F
authors.lastname: Krombach
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D018496:Hyperoxia / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008252:Macaca fascicularis; D016177:Macrophage-1 Antigen / Q000096:biosynthesis*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha