Role of the leukocyte-adhesion molecule L-selectin in experimental autoimmune encephalomyelitis.
L-selectin is an adhesion molecule expressed on T cells and monocytes. It mediates rolling--the initial step of transendothelial migration. In this study, we investigated the role of L-selectin in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced in Lewis rats by active sensitization with myelin basic protein (MBP-EAE), or by adoptive transfer using MBP specific T cells (AT-EAE). Treatment with HRL3, a monoclonal antibody to L-selectin, and its F(ab')2 fragments efficiently suppressed MBP-EAE, and had a mild inhibitory effect on AT-EAE. Histological examination revealed a marked reduction of inflammatory infiltrates after treatment with HRL3. Administration of the control antibody HRL4 did not significantly alter the course of the disease. HRL3 caused T-cell depletion in the draining lymph nodes and spleen and a downregulation of L-selectin expression on T cells. We conclude that L-selectin-dependent mechanisms are involved in the pathogenesis of EAE. Modulation of L-selectin in vivo by antibodies or by competitive antagonists could be a novel therapeutic approach to autoimmune diseases of the central nervous system.
Archelos
J J
JJ
Department of Neurology, Clinical Research Group for Multiple Sclerosis, Julius-Maximilians-Universität Würzburg, Germany. archelos@mpipsykl.mpg.de
Jung
S
S
Rinner
W
W
Lassmann
H
H
Miyasaka
M
M
Hartung
H P
HP
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D006224:Cricetinae; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D019041:L-Selectin / Q000502:physiology*; D008198:Lymph Nodes / Q000276:immunology; D009443:Neuritis / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D019041:L-Selectin