title: Decreased alveolar oxygen induces lung inflammation.
abstract: 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.
authors.affiliation: Institute of Physiology, Department of Surgery, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Madjdpour
authors.forename: U R
authors.initials: UR
authors.lastname: Jewell
authors.forename: S
authors.initials: S
authors.lastname: Kneller
authors.forename: U
authors.initials: U
authors.lastname: Ziegler
authors.forename: R
authors.initials: R
authors.lastname: Schwendener
authors.forename: C
authors.initials: C
authors.lastname: Booy
authors.forename: L
authors.initials: L
authors.lastname: Kläusli
authors.forename: T
authors.initials: T
authors.lastname: Pasch
authors.forename: R C
authors.initials: RC
authors.lastname: Schimmer
authors.forename: B
authors.initials: B
authors.lastname: Beck-Schimmer
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002199:Capillary Permeability; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018836:Inflammation Mediators / Q000378:metabolism; D008171:Lung Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D011014:Pneumonia / Q000209:etiology*; D011650:Pulmonary Alveoli; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D012709:Serum Albumin; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha