title: Expression of lung vascular and airway ICAM-1 after exposure to bacterial lipopolysaccharide.
abstract: Airway instillation of bacterial lipopolysaccharide (LPS) into rat lungs induces neutrophil accumulation, which is known to be intercellular adhesion molecule-1 (ICAM-1)-dependent. In the present study, ICAM-1 messenger RNA (mRNA) of whole lung was found to increase by 20-fold in this inflammatory model. This increase was reduced by 81% after treatment of animals with anti-tumor necrosis factor-alpha (TNF-alpha) antibody and by 37% after treatment with anti-interleukin-1 (IL-1) antibody. The same interventions reduced whole-lung ICAM-1 protein by 85% and 25%, respectively. The studies were extended to assess the locale in lung of ICAM-I upregulation. Lung vascular ICAM-1 content, which was assessed by vascular fixation of [125I]anti-ICAM-1, rose 4-fold after airway instillation of LPS. This rise was also TNF-alpha-dependent. Under the same experimental conditions, fixation of [125I]anti-ICAM-1 to airway surfaces increased 11-fold in a TNF-alpha-dependent manner. In situ hybridization and immunohistochemical analyses of lung tissue revealed ICAM-1 upregulation in the bronchiolar epithelium and in peribronchiolar smooth muscle. Soluble ICAM-1 could also be detected in bronchoalveolar lavage fluids (BALFs) of animals after intratracheal instillation of LPS. Retrieved alveolar macrophages showed a small, significant, and transient increase in surface expression of ICAM-1. These data indicate, at the very least, a dual compartmentalized (vascular and airway) upregulation of ICAM-1 after airway instillation of LPS. This upregulation requires TNF-alpha and IL-1. The functional significance of upregulated airway ICAM-1 remains to be determined.
authors.affiliation: Institute for Anaesthesiology and Department of Surgery, University of Zurich Medical School, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Beck-Schimmer
authors.forename: R C
authors.initials: RC
authors.lastname: Schimmer
authors.forename: R L
authors.initials: RL
authors.lastname: Warner
authors.forename: H
authors.initials: H
authors.lastname: Schmal
authors.forename: G
authors.initials: G
authors.lastname: Nordblom
authors.forename: C M
authors.initials: CM
authors.lastname: Flory
authors.forename: M E
authors.initials: ME
authors.lastname: Lesch
authors.forename: H P
authors.initials: HP
authors.lastname: Friedl
authors.forename: D J
authors.initials: DJ
authors.lastname: Schrier
authors.forename: P A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western; D015870:Gene Expression / Q000187:drug effects; D017403:In Situ Hybridization; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply* / Q000737:chemistry* / Q000166:cytology; D016676:Macrophages, Alveolar / Q000737:chemistry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000187:drug effects; D009504:Neutrophils / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000906:Antibodies; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1