MODULATION OF THE EXPRESSION OF INTEGRINS ON GLIAL-CELLS DURING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - A CENTRAL ROLE FOR TNF-ALPHA

Integrins comprise a group of adhesion receptors involved in cell-cell and cell-extracellular matrix interactions, Evidence is accumulating that integrins expressed on mononuclear cells play a central role in t he induction of autoimmune diseases of the central nervous system. The effects of integrins on glial cell behavior, myelination, and angioge nesis suggest that they may also have a role in resolving inflammation in the nervous system and in promoting tissue repair. We investigated the temporospatial expression of integrins in the rat central nervous system during the course of experimental autoimmune encephalomyelitis , an animal model of multiple sclerosis, A higher expression of av- an d beta 4-integrin subunits in astrocytes and alpha 2 integrin in oligo dendrocytes was observed in active lesions of experimental autoimmune encephalomyelitis, in comparison with controls, Proinflammatory cytoki nes, primarily TNF-alpha, also enhanced av, beta 4, and alpha 2 expres sion in purified glial cells ex vivo, Furthermore, we observed that th e expression of some integrin subunits was modulated in the cerebral v asculature during inflammation, Our results suggest an active role for glial and vascular integrins in the regulation of autoimmune diseases of the central nervous system, opening an avenue for new potential im munotherapies.