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Prevention of a chronic progressive form of experimental autoimmune encephalomyelitis by an antibody against mucosal addressin cell adhesion molecule‐1, given early in the course of disease progression
Author(s) -
Kanwar Jagat R,
Kanwar Rupinder K,
Wang Dongmao,
Krissansen Geoffrey W
Publication year - 2000
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1046/j.1440-1711.2000.00947.x
Subject(s) - addressin , experimental autoimmune encephalomyelitis , cell adhesion molecule , immunology , antibody , cell adhesion , high endothelial venules , medicine , multiple sclerosis , lymphocyte homing receptor , encephalomyelitis , integrin , cancer research , lymphocyte , biology , cell , receptor , genetics
A role for α4 and β7 integrins in mediating leucocyte entry into the central nervous system in the multiple sclerosis (MS)‐like disease experimental autoimmune encephalomyelitis (EAE) has been demonstrated. However, the individual contributions of their respective ligands mucosal addressin cell adhesion molecule‐1 (MAdCAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1) and E‐cadherin expressed on the blood–brain barrier has not been determined. In the present paper, it is shown that an antibody directed against MAdCAM‐1, the preferential ligand for α4β7, effectively prevented the development of a progressive, non‐remitting, form of EAE, actively induced by injection of myelin oligodendrocyte glycoprotein peptide (MOG 35–55 ) autoantigen. Combinational treatment with both anti‐MAdCAM‐1, VCAM‐1, and intercellular adhesion molecule‐1 (ICAM‐1) (ligand for integrin lymphocyte function‐associated antigen (LFA)‐1) mAbs led to more rapid remission than that obtained with anti‐MAdCAM‐1 antibody alone. However, neither MAdCAM‐1 monotherapy, nor combinational antibody blockade was preventative when administered late in the course of disease progression. In conclusion, MAdCAM‐1 plays a major contributory role in the progression of chronic EAE and is a potential therapeutic target for the treatment of MS. Critically, antivascular addressin therapy must be given early in the course of disease prior to the establishment of irreversible damage if it is to be effective, as a single treatment modality.