Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1-deficient mice

J Clin Invest. 2002 Feb;109(3):383-92. doi: 10.1172/JCI13595.


Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31), a 130-kDa glycoprotein member of the Ig superfamily of transmembrane proteins, is expressed on endothelial cells, platelets, and subsets of leukocytes. It functions as a cell adhesion molecule as well as a scaffolding molecule capable of modulating cellular signaling pathways. In this study, using PECAM-1-deficient (KO) mice, as well as cells derived from these mice, we demonstrate that the absence of PECAM-1 expression is associated with an early onset of clinical symptoms during experimental autoimmune encephalomyelitis (EAE), a mouse model for the human autoimmune disease multiple sclerosis. During EAE, mononuclear cell extravasation and infiltration of the CNS occur at earlier time points in PECAM-KO mice than in wild-type mice. In vitro, T lymphocyte transendothelial migration across PECAM-KO endothelial cells is enhanced, regardless of expression of PECAM-1 on transmigrating T cells. Additionally, cultured PECAM-KO endothelial cells exhibit prolonged permeability changes in response to histamine treatment compared with PECAM-1-reconstituted endothelial cells. Lastly, we demonstrate an exaggerated and prolonged CNS vascular permeability during the development of EAE and a delay in restoration of dermal vascular integrity following histamine challenge in PECAM-KO mice.

Publication types

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

MeSH terms

  • Animals
  • Capillary Permeability / drug effects
  • Capillary Permeability / physiology*
  • Cell Movement
  • Central Nervous System / pathology
  • Encephalomyelitis, Autoimmune, Experimental / etiology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Endothelium, Vascular / pathology
  • Histamine / pharmacology
  • Humans
  • In Vitro Techniques
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism*
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology


  • Platelet Endothelial Cell Adhesion Molecule-1
  • Histamine