The extracellular matrix in multiple sclerosis lesions.
Receptor-mediated recognition of extracellular matrix (ECM) molecules transduces intracellular signals that determine many cellular behaviors under normal and pathological conditions. This review briefly describes the major central nervous system (CNS) white matter ECM molecules and their receptors, the mechanisms by which the ECM may be altered in multiple sclerosis (MS) lesions, and potential roles for inflammatory and CNS resident cell interactions with specific ECM molecules in these lesions. In acute lesions, ECM recognition and cell signaling contribute to leukocyte migration through blood vessel walls, and within the CNS, through leukocyte and CNS resident cell immune activation and demyelination. An abnormal ECM in chronic MS lesions may preclude ECM-dependent developmental processes that lead to remyelination and axon regeneration. Thus, the composition of the ECM and the cellular recognition of its individual components may be critical to the pathogenesis of all stages of MS. An understanding of these complex interactions may lead to additional strategies for intervention and the promotion of reparative processes in MS patients.
Sobel
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RA
Pathology and Laboratory Services, Veterans Administration Health Care System, Palo Alto, Calif 94304, USA.
D001369:Axons / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction
D016326:Extracellular Matrix Proteins; D011956:Receptors, Cell Surface; C052131:extracellular matrix receptor