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

Abstract

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.

• Authors: Donnasue Graesser, Anna Solowiej, Monika Bruckner, Emily Osterweil, Amy Juedes, Sandra Davis, Nancy H Ruddle, Britta Engelhardt, Joseph A Madri
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 109 Issue 3 Pg. 383-92 (Feb 2002) ISSN: 0021-9738 [Print] United States
• PMID: 11827998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Platelet Endothelial Cell Adhesion Molecule-1
• Histamine

Topics

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