Keszthelyi E, Karlik S, Hyduk S, Rice G P, Gordon G, Yednock T, Horner H
Department of Physiology, University of Western Ontario, London, Canada.
Neurology. 1996 Oct;47(4):1053-9. doi: 10.1212/wnl.47.4.1053.
The leukocyte integrin receptor, alpha 4 beta 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 alpha 4 beta 1/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 alpha 4 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-alpha 4 treatment. These results demonstrate an essential role for alpha 4 beta 1 interactions throughout active EAE and illustrate the difference between reversible clinical deficits caused by edema and irreversible deficits associated with demyelination.
白细胞整合素受体α4β1及其内皮细胞配体血管细胞黏附分子1，在实验性自身免疫性脑脊髓炎（EAE）中伴随中枢神经系统损伤的白细胞迁移过程中似乎至关重要。在本研究中，通过观察疾病发作后长达1个月的抗体介导的疾病逆转，确定了α4β1/血管细胞黏附分子1在EAE中的持续作用。用抗α4整合素单克隆抗体GG5/3进行有限治疗，导致临床和组织病理学体征均显著降低。在同型对照实验中未观察到这种情况。在进行性疾病的后期，未对抗α4治疗6天产生反应的动物出现广泛的脱髓鞘。这些结果证明了α4β1相互作用在整个活动性EAE中的重要作用，并说明了由水肿引起的可逆性临床缺陷与与脱髓鞘相关的不可逆缺陷之间的差异。
