Hyduk S J, Karlik S J
Department of Physiology, London Health Sciences Centre, University of Western Ontario, Canada.
J Neuropathol Exp Neurol. 1998 Jun;57(6):602-14. doi: 10.1097/00005072-199806000-00007.
Experimental allergic encephalomyelitis (EAE) is an autoimmune, demyelinating disorder of the central nervous system induced in susceptible animals as a model for the human disease multiple sclerosis. Antibodies against the leukocyte adhesion molecule alpha4 integrin have been shown to prevent and reverse acute and chronic EAE of the guinea pig. The results presented in this paper implicate apoptosis as the mechanism of reversal of EAE following treatment with anti-alpha4 integrin antibody. Apoptotic cells were observed in the central nervous system (CNS) throughout chronic-progressive EAE of the guinea pig in the absence of clinical recovery. Many of the apoptotic cells were identified as T cells using immunohistochemistry. Similarly, apoptotic cells were present in the CNS of animals during anti-alpha4 integrin-mediated recovery from acute and chronic disease. Therefore, anti-alpha4 integrin-mediated recovery from EAE is due to the prevention of the influx of new inflammatory cells into the CNS that are required to replace those undergoing apoptosis.
实验性自身免疫性脑脊髓炎（EAE）是一种自身免疫性脱髓鞘疾病，在易感动物中诱发，作为人类疾病多发性硬化症的模型。针对白细胞粘附分子α4整合素的抗体已被证明可预防和逆转豚鼠的急性和慢性EAE。本文给出的结果表明，细胞凋亡是抗α4整合素抗体治疗后EAE逆转的机制。在豚鼠慢性进行性EAE的整个过程中，在中枢神经系统（CNS）中观察到凋亡细胞，且无临床恢复。使用免疫组织化学方法鉴定出许多凋亡细胞为T细胞。同样，在抗α4整合素介导的急性和慢性疾病恢复过程中，动物的中枢神经系统中也存在凋亡细胞。因此，抗α4整合素介导的EAE恢复是由于阻止了新的炎症细胞流入中枢神经系统，而这些新的炎症细胞是替代正在经历凋亡的细胞所必需的。
