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 markers not expressed by quiescent EC. These surface markers augment adhesion reactions and leukocyte migration. We examined microvessel EC activation longitudinally in experimental autoimmune encephalomyelitis (EAE) in Lewis rats. CNS microvessels were isolated at 0, 3, 7, 12, 20, and 30 days post-inoculation (PI). Normal and CFA-injected rat microvessels do not express activation antigens (Ag). Increased expression of major histocompatibility complex (MHC) class II molecule and intercellular adhesion molecule-1 (ICAM-1) were detected on CNS microvessels from immunized rats at 7 days PI, prior to development of clinical signs, and at 12 days PI. Enhanced MHC class I molecule was seen only at 12 days. MHC class II molecule expression was focally expressed along microvessel fragments. By 20 days PI, EC did not exhibit increased levels of any of the markers tested. Perivascular cells (possibly pericytes), however, were found to express MHC class II molecule and ICAM-1 up to 30 days PI. During the recovery phase isolated CNS microvessels from MBP-immunized rats were unresponsive to IFN gamma-mediated endothelial activation. Unresponsiveness was independent of IFN gamma concentration. These results suggest that the endothelium is restored to functional quiescence during the recovery phase of acute EAE.
Dore-Duffy
P
P
Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Balabanov
R
R
Rafols
J
J
Swanborg
R H
RH
D000818:Animals; D002196:Capillaries / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000502:physiology
D016207:Cytokines; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma