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 the induction of autoimmune diseases of the central nervous system. The effects of integrins on glial cell behavior, myelination, and angiogenesis 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 alpha v- and beta 4-integrin subunits in astrocytes and alpha 2 integrin in oligodendrocytes was observed in active lesions of experimental autoimmune encephalomyelitis, in comparison with controls. Proinflammatory cytokines, primarily TNF-alpha, also enhanced alpha v, beta 4, and alpha 2 expression in purified glial cells ex vivo. Furthermore, we observed that the expression of some integrin subunits was modulated in the cerebral vasculature 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 immunotherapies.
Previtali
S C
SC
Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
Archelos
J J
JJ
Hartung
H P
HP
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016023:Integrins / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values; D013116:Spinal Cord / Q000098:blood supply; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D016023:Integrins; D014409:Tumor Necrosis Factor-alpha