Expression of lung vascular and airway ICAM-1 after exposure to bacterial lipopolysaccharide

Am J Respir Cell Mol Biol. 1997 Sep;17(3):344-52. doi: 10.1165/ajrcmb.17.3.2861.


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.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Blotting, Western
  • Gene Expression / drug effects
  • In Situ Hybridization
  • Intercellular Adhesion Molecule-1 / analysis
  • Intercellular Adhesion Molecule-1 / genetics*
  • Intercellular Adhesion Molecule-1 / immunology
  • Interleukin-1 / immunology
  • Lipopolysaccharides / pharmacology*
  • Lung / blood supply*
  • Lung / chemistry*
  • Lung / cytology
  • Macrophages, Alveolar / chemistry
  • Male
  • Muscle, Smooth, Vascular / chemistry
  • Muscle, Smooth, Vascular / drug effects
  • Neutrophils / immunology
  • RNA, Messenger / analysis
  • Rats
  • Rats, Inbred Strains
  • Time Factors
  • Tumor Necrosis Factor-alpha / immunology
  • Up-Regulation / drug effects


  • Antibodies
  • Interleukin-1
  • Lipopolysaccharides
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1