title: Shift toward an alternatively activated macrophage response in lungs of NO2-exposed rats.
abstract: Inflammatory mechanisms are thought to play an important role in the pathogenesis of acute and chronic obstructive pulmonary diseases. In a rat inhalation model using continuous exposure to 10 ppm nitrogen dioxide for 1, 3, and 20 d, we investigated the inflammatory response with particular focus on the activation state of alveolar macrophages. Whereas the number of inflammatory cells and total protein concentration were increased in the bronchoalveolar lavage (BAL), the amount of the proinflammatory cytokine tumor necrosis factor-alpha was markedly reduced with increasing exposure time. In contrast, interleukin (IL)-10 and IL-6 were found at elevated levels and intracellular amounts of suppressor of cytokine signaling-3 protein increased in BAL cells. Upon in vitro lipopolysaccharide stimulation, BAL cells revealed reduced capability to produce the proinflammatory mediators tumor necrosis factor-alpha, IL-1 beta, and nitric oxide, but showed markedly increased transcription and protein release for IL-10. In addition, elevated levels of IL-6, scavenger receptor B, and suppressor of cytokine signaling-3 mRNA were detected in BAL cells from exposed animals. Analyses of highly purified alveolar macrophages indicated that changes in the activation state of these cells were responsible for the observed effects. In conclusion, a priming toward development of the alternatively activated macrophage phenotype occurred in the lungs of rats following nitrogen dioxide inhalation.
authors.affiliation: Institute of Immunology, Department of Pathology, Laboratory of Lung Cell Biology, Philipps University Marburg, Marburg, Germany. garn@mailer.uni-marburg.de
authors.forename: Holger
authors.initials: H
authors.lastname: Garn
authors.forename: Anette
authors.initials: A
authors.lastname: Siese
authors.forename: Sabine
authors.initials: S
authors.lastname: Stumpf
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barth
authors.forename: Bernd
authors.initials: B
authors.lastname: Müller
authors.forename: Diethard
authors.initials: D
authors.lastname: Gemsa
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002478:Cells, Cultured; D004926:Escherichia coli; D016753:Interleukin-10 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D009585:Nitrogen Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D011971:Receptors, Immunologic / Q000032:analysis; D012097:Repressor Proteins; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D011506:Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D012097:Repressor Proteins; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D009585:Nitrogen Dioxide