EXPRESSION OF IMMUNOLOGICALLY RELEVANT ENDOTHELIAL-CELL ACTIVATION ANTIGENS ON ISOLATED CENTRAL-NERVOUS-SYSTEM MICROVESSELS FROM PATIENTS WITH MULTIPLE-SCLEROSIS

Activation of the vascular endothelium is thought to be an important f acet of inflammation, thrombosis, and vasculitis. Activated endothelia l cells express a number of immunologically relevant surface markers n ot expressed by normal endothelial cells. Many of these surface antige ns are thought ro augment adhesion reactions and migration. Our result s show that endothelial activation may play a central role in the path ogenesis of multiple sclerosis (MS). Normal human central nervous syst em microvessels isolated from autopsy material do not express endothel ial cell activation markers, including the adhesion proteins vascular cell adhesion molecule-1 (VCAM-1) and endothelial cell leukocyte adhes ion molecule-1 (E-selectin/ELAM-1). They exhibit little to no constitu tive expression of immunoreactive intercellular adhesion molecule-1 (I CAM-1) or the urokinase plasminogen activator receptor. Control microv essels exhibit no major histocompatibility complex (MHC) class II anti gen. MS microvessels express significant levels of MHC class II antige ns, ICAM-1, VCAM-1, and urokinase plasminogen activator receptor. E-se lectin was expressed by 3 of 5 MS brains tested. Histologically unaffe cted areas of MS brain expressed less VCAM-1, ICAM-1, and E-selectin t han did microvessels from periplaque zones. However, MHC class II anti gens and urokinase plasminogen activator receptor were increased in ar eas exhibiting little to no evidence of leukocyte infiltration. When m icrovessels were examined for dual expression of activation markers, w e found that in periplaque areas, 50% of microvessels coexpressed HLA- DR and VCAM-1, 28% of microvessels coexpressed HLA-DR and urokinase pl asminogen activator receptor, and 43% of microvessels coexpressed HLA- DR and ICAM-1.