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NEUROLOGY 1996;47:1053-1059
© 1996 American Academy of Neurology

Evidence for a prolonged role of alpha sub 4 integrin throughout active experimental allergic encephalomyelitis

E. Keszthelyi, BSc, S. Karlik, PhD, S. Hyduk, BSc, G.P.A. Rice, MD, G. Gordon, BA, T. Yednock, PhD and H. Horner, PhD

From the Departments of Physiology (Drs. Keszthelyi, Karlik, and Hyduk), Diagnostic Radiology and Nuclear Medicine (Dr. Karlik), and Clinical Neurological Sciences (Drs. Karlik and Rice), University of Western Ontario, London, Ontario, Canada; and Athena Neurosciences (Drs. Gordon, Yednock, and Horner), South San Francisco, CA.
Funding for this work was provided by the Multiple Sclerosis Society of Canada.
Received September 12, 1995. Accepted in final form February 19, 1996.
Address correspondence and reprint requests to Dr. Stephen J. Karlik, Departments of Diagnostic Radiology and Nuclear Medicine, University Hospital, 339 Windermere Road, London, Ontario, N6A 5A5, Canada.

The leukocyte integrin receptor, alpha sub 4 beta sub 1, and its endothelial cell ligand, vascular cell adhesion molecule 1, appear to be of critical importance in the leukocyte trafficking that accompanies CNS damage in experimental allergic encephalomyelitis (EAE).In this study, the persistence of the role for alpha4 beta1/VCAM-1 in EAE was established by observing antibody-mediated disease reversal up to 1 month following disease onset. Limited treatment with a monoclonal antibody against alpha4 integrin, GG5/3, resulted in a significant decrease in both clinical and histopathologic signs. This was not observed in isotype control experiments. In the latter phase of progressive disease, widespread demyelination occurred in the animals that did not respond to 6 days of anti-alpha4 treatment. These results demonstrate an essential role for alpha4 beta1 interactions throughout active EAE and illustrate the difference between reversible clinical deficits caused by edema and irreversible deficits associated with demyelination.

NEUROLOGY 1996;47: 1053-1059




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