Alpha4-integrin-VCAM-1 binding mediates G protein-independent capture of encephalitogenic T cell blasts to CNS white matter microvessels

J Clin Invest. 2001 Aug;108(4):557-65. doi: 10.1172/JCI12440.

Abstract

Direct in vivo evidence is still lacking for alpha4-integrin-mediated T cell interaction with VCAM-1 on blood-brain barrier-endothelium in experimental autoimmune encephalomyelitis (EAE). To investigate a possible alpha4-integrin-mediated interaction of encephalitogenic T cell blasts with VCAM-1 on the blood-brain barrier white matter endothelium in vivo, we have developed a novel spinal cord window preparation that enabled us to directly visualize CNS white matter microcirculation by intravital fluorescence videomicroscopy. Our study provides the first in vivo evidence that encephalitogenic T cell blasts interact with the spinal cord white matter microvasculature without rolling and that alpha4-integrin mediates the G protein-independent capture and subsequently the G protein-dependent adhesion strengthening of T cell blasts to microvascular VCAM-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism*
  • Autoimmune Diseases / pathology
  • Blood-Brain Barrier / physiology*
  • Capillaries / pathology
  • Cell Adhesion
  • Chemotaxis, Leukocyte / physiology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Female
  • GTP-Binding Proteins / antagonists & inhibitors
  • GTP-Binding Proteins / physiology
  • Integrin alpha4
  • Mice
  • Microcirculation
  • Microscopy, Fluorescence
  • Microscopy, Video
  • Nervous System Autoimmune Disease, Experimental
  • Protein Binding
  • Skin Window Technique
  • Spinal Cord / blood supply*
  • Spinal Cord / pathology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • Vascular Cell Adhesion Molecule-1 / metabolism*
  • Virulence Factors, Bordetella / genetics
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Antigens, CD
  • Vascular Cell Adhesion Molecule-1
  • Virulence Factors, Bordetella
  • Integrin alpha4
  • GTP-Binding Proteins