Brain, Vol 121, Issue 7 1257-1266, Copyright © 1998 by Oxford University Press
U Enders, R Lobb, RB Pepinsky, HP Hartung, KV Toyka and R Gold
We have investigated the functional role of very late antigen-4 [VLA-4
(alpha4/beta1) integrin] and vascular cell adhesion molecule-1 (VCAM-1) in
experimental autoimmune neuritis (EAN), an animal model of the
Guillain-Barre syndrome, using neutralizing monoclonal antibodies (mAbs) as
probes. Disease was induced by intravenous adoptive transfer of P2 specific
T cells (AT-EAN), or by immunization with bovine myelin (active EAN).
Preventive treatment with 500 microg anti-VLA-4 mAb (TA- 2) or with an
isotype control antibody was given in AT-EAN 4 h before cell transfer and
at day 3. Intravenous injection of 500 microg anti- VCAM-1 mAb (5F10) or a
corresponding isotype control was given in AT- EAN 4 h before disease
induction, and at days 2, 4 and 6. Preventive treatment of active EAN with
mAb to VLA-4 or VCAM-1 was performed at days 5, 9 and 13. On
immunohistochemical examination, VCAM-1 in sciatic nerve was found to be
upregulated at early stages of EAN (days 3-5 after T-cell transfer), whilst
no expression was noted in healthy controls. In both EAN models, blockade
of VLA-4 markedly attenuated disease severity. Blockade of VCAM-1 also
significantly ameliorated the disease course and diminished T-cell
infiltration in sciatic nerve, but to a lesser degree. These experiments
demonstrate the critical role of VLA-4 in the pathogenesis of EAN and show
that upregulation of VCAM-1 expression contributes, at least in part, to
the progression of the disease in the early stages. Future studies are
needed to assess the potential contribution of other VLA-4 ligands.
ARTICLES
The role of the very late antigen-4 and its counterligand vascular cell adhesion molecule-1 in the pathogenesis of experimental autoimmune neuritis of the Lewis rat
Department of Neurology, Julius-Maximilians Universitat, Wurzburg, Germany.
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