Thy-1 induced on rat endothelium regulates vascular permeability at sites of inflammation

Int Immunol. 1995 Dec;7(12):1939-47. doi: 10.1093/intimm/7.12.1939.

Abstract

We investigated the role of surface adhesion molecules on endothelial cells in regulating vascular permeability, in vitro and in vivo. Cultured rat endothelial cells (REC) express Thy-1, intercellular adhesion molecule-1 (ICAM-1), CD44 and RT1A. Permeability of albumin across the REC monolayer increased through the interaction of Thy-1 and anti-Thy-1 mAb, but not through ICAM-1 and anti-ICAM-1, CD44 and anti-CD44, and RT1A and anti-RT1A mAb. This anti-Thy-1-effect was completely inhibited when the calmodulin antagonist W-7 and the protein kinase inhibitor H-7 was combined, while the IL-6-mediated increase in REC permeability was blocked by either W-7 or H-7, independently. The anti-Thy-1-mediated permeability increase was additively augmented when IL-6 was admixed. These data suggest that intracellular signaling pathways of anti-Thy-1- and IL-6-mediated permeability regulation may be overlapping to some extent but are largely independent. As anti-Thy-1-treatment generated rearrangement of vimentin filaments within REC, alteration of the cytoskeleton distribution may possibly correlate with the regulation of permeability. Although Thy-1-expression on rat vascular endothelium in vivo was not evident, it was induced at sites of Freund's complete adjuvant-induced dermatitis. The administered anti-Thy-1 mAb exclusively located on vascular endothelial surface at the sites of inflammation. Vascular permeability in inflamed skin tissues was significantly augmented when anti-Thy-1 but not anti-ICAM-1, anti-CD44 or anti-RT1A mAb was administered i.v., without affecting populations of inflammatory cells. The collective evidence suggests that Thy-1 induced on rat endothelium is one important regulatory event in vascular permeability at sites of inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Capillary Permeability / immunology*
  • Capillary Permeability / physiology
  • Cells, Cultured
  • Cytoskeleton / ultrastructure
  • Endothelium, Vascular / immunology*
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology*
  • Histocompatibility Antigens / physiology
  • Hyaluronan Receptors / physiology
  • In Vitro Techniques
  • Inflammation / immunology*
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Intercellular Adhesion Molecule-1 / physiology
  • Male
  • Mice
  • Rats
  • Rats, Inbred Strains
  • Thy-1 Antigens / biosynthesis
  • Thy-1 Antigens / physiology*

Substances

  • Antibodies, Monoclonal
  • Histocompatibility Antigens
  • Hyaluronan Receptors
  • Thy-1 Antigens
  • histocompatibility antigens RT, rat
  • Intercellular Adhesion Molecule-1