Article: article from journal or magazin.
Decreased alveolar oxygen induces lung inflammation.
American Journal of Physiology. Lung Cellular and Molecular Physiology
Publication types: Journal Article
Molecular mechanisms of the inflammatory reaction in hypoxia-induced lung injury are not well defined. Therefore, effects of alveolar hypoxia were studied in rat lungs, exposing rats to 10% oxygen over periods of 1, 2, 4, 6, and 8 h. An increase in the number of macrophages in bronchoalveolar lavage fluid of hypoxic animals was shown between 1 and 8 h. Extravasation of albumin was enhanced after 1 h and remained increased throughout the study period. NF-kappaB-binding activity as well as mRNA for TNF-alpha, macrophage inflammatory protein (MIP)-1beta, and monocyte chemoattractant protein (MCP)-1 were increased within the first 2 h of exposure to hypoxia. Hypoxia-inducible factor (HIF)-1alpha and intercellular adhesion molecule (ICAM)-1 mRNA were upregulated between 1 and 6 h. Elimination of alveolar macrophages by intratracheal application of liposome-encapsulated clodronate led to a decreased expression of NF-kappaB binding activity, HIF-1alpha, TNF-alpha, ICAM-1, and MIP-1beta. In summary, alveolar hypoxia induced macrophage recruitment, an increase in albumin leakage, and enhanced expression of inflammatory mediators, which were mainly macrophage dependent. Alveolar macrophages appear to have a prominent role in the inflammatory response in hypoxia-induced lung injury and the related upregulation of inflammatory mediators.
Animals, Anoxia/complications, Anoxia/metabolism, Bronchoalveolar Lavage Fluid/cytology, Capillary Permeability, Chemokine CCL2/genetics, Chemokine CCL2/metabolism, Hypoxia-Inducible Factor 1, alpha Subunit, Inflammation Mediators/metabolism, Lung Diseases/complications, Lung Diseases/metabolism, Macrophages, Alveolar/pathology, Male, NF-kappa B/metabolism, Neutrophils/physiology, Pneumonia/etiology, Pulmonary Alveoli, RNA, Messenger/metabolism, Rats, Rats, Sprague-Dawley, Serum Albumin/metabolism, Transcription Factors/genetics, Tumor Necrosis Factor-alpha/genetics, Tumor Necrosis Factor-alpha/metabolism
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