Distinct roles for matrix metalloproteinase-2 and alpha4 integrin in autoimmune T cell extravasation and residency in brain parenchyma during experimental autoimmune encephalomyelitis.

Abstract

Expression of alpha4 integrin by auto-reactive T cells is critical for their ability to induce EAE, an autoimmune disease of the central nervous system in mice, used as a model to study human multiple sclerosis. Having previously identified one role for alpha4 integrin in adhesion-mediated induction of matrix metalloproteinase-2 (MMP-2), an enzyme that degrades the subendothelial basement membrane matrix, we investigated independent roles for MMP-2 and alpha4 integrin during EAE. The data suggest that expression of alpha4 integrin by auto-reactive T cells is important not only in mediating MMP-2 induction to facilitate entry into the CNS, but also plays a role in maintaining residency within the CNS.

• Authors: D Graesser, S Mahooti, J A Madri
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 109 Issue 2 Pg. 121-31 (Sep 22 2000) ISSN: 0165-5728 [Print] Netherlands
• PMID: 10996214 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD
• Autoantigens
• Dipeptides
• N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
• Protease Inhibitors
• Integrin alpha4
• Matrix Metalloproteinase 2

Topics

• Animals
• Antigens, CD (immunology)
• Autoantigens (immunology)
• Brain (cytology, immunology, metabolism)
• Cell Movement (drug effects, immunology)
• Clone Cells
• Dipeptides (pharmacology)
• Encephalomyelitis, Autoimmune, Experimental (etiology, immunology, metabolism)
• Endothelium, Vascular (cytology, enzymology, immunology)
• Integrin alpha4
• Matrix Metalloproteinase 2 (genetics, immunology, metabolism)
• Mice
• Mice, Inbred Strains
• Mice, Transgenic
• Multiple Sclerosis (etiology, immunology, metabolism)
• Protease Inhibitors (pharmacology)
• Rats
• T-Lymphocytes (cytology, immunology)