RECOVERY PHASE OF ACUTE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN RATS CORRESPONDS TO DEVELOPMENT OF ENDOTHELIAL-CELL UNRESPONSIVENESS TO INTERFERON-GAMMA ACTIVATION

Activation of the vascular endothelium is important in the development of inflammation, Activated endothelial cells (EC) express surface mar kers not expressed by quiescent EC, These surface markers augment adhe sion reactions and leukocyte migration, We examined microvessel EC act ivation longitudinally in experimental autoimmune encephalomyelitis (E AE) in Lewis rats, CNS microvessels were isolated at 0, 3, 7, 12, 20, and 30 days post-inoculation (PI), Normal and CPA-injected rat microve ssels do not express activation antigens (Ag), Increased expression of major histocompatibility complex (MHC) class II molecule and intercel lular adhesion molecule-1 (ICAM-1) were detected on CNS microvessels f rom immunized rats at 7 days PI, prior to development of clinical sign s, and at 12 days PI, Enhanced MBC class I molecule was seen only at 1 2 days, MHC class II molecule expression was focally expressed along m icrovessel fragments, By 20 days PI, EC did not exhibit increased leve ls of any of the markers tested, Perivascular cells (possibly pericyte s), however, were found to express MHC class II molecule and ICAM-1 up to 30 days PI. During the recovery phase isolated CNS microvessels fr om MBP-immunized rats were unresponsive to IFN gamma-mediated endothel ial activation. Unresponsiveness was independent of IFN gamma concentr ation, These results suggest that the endothelium is restored to funct ional quiescence during the recovery phase of acute EAE. (C) 1996 Wile y-Liss, Inc.