Cytokine-induced VCAM-1 and ICAM-1 expression in different organs of the mouse

J Immunol. 1997 Feb 15;158(4):1825-32.

Abstract

The dual radiolabeled mAb technique was used to quantify the constitutive and induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the microvasculature of different organs of the mouse. The constitutive expression of both adhesion molecules varied significantly between tissues, with ICAM-1 levels consistently higher than VCAM-1 in all tissues studied. Following systemic administration of endotoxin (LPS), an increased surface expression of both adhesion molecules occurred in most organs, with the largest increases for ICAM-1 (2 to 3x increase) noted in the heart, small intestine, and brain, while heart and small intestine exhibited the largest increases in LPS-induced VCAM-1 expression (2 to 5x increase). These responses occurred in the face of an unaltered expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) in all tissues. TNF-alpha also elicited an increased expression of both adhesion molecules, with initial increases noted at 2 to 5 h, peak levels at 5 to 9 h, and a sustained elevation above baseline at 24 h. The TNF-alpha-induced increases in both ICAM-1 and VCAM-1 were dose dependent, with significant up-regulation noted at 5 microg/kg and maximal increases occurring at 10 to 25 microg/kg. These studies indicate that while there are significant quantitative differences in constitutive and induced expression of murine ICAM-1 and VCAM-1, the kinetics and dose-response characteristics of the two adhesion molecules to TNF-alpha are qualitatively similar.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cytokines / pharmacology*
  • Dose-Response Relationship, Immunologic
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Intercellular Adhesion Molecule-1 / chemistry
  • Intercellular Adhesion Molecule-1 / genetics
  • Kinetics
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Specificity / immunology
  • Platelet Endothelial Cell Adhesion Molecule-1 / biosynthesis
  • Platelet Endothelial Cell Adhesion Molecule-1 / drug effects
  • Solubility
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / biosynthesis*
  • Vascular Cell Adhesion Molecule-1 / chemistry

Substances

  • Cytokines
  • Lipopolysaccharides
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1