通过对α4β1整合素的抗体预防实验性自身免疫脑膜炎
T A Yednock1, C Cannon, L C Fritz
1Athena Neurosciences, South San Francisco, California.
Nature
|March 5, 1992
概括
研究人员确定alpha 4 beta 1整体因在实验性自身免疫脑膜炎 (EAE) 期间对于白细胞进入中枢神经系统至关重要. 阻止这种整合素可能为中枢神经系统炎症性疾病 (如多发性硬化症) 提供新的治疗方法.
科学领域:
- 神经免疫学 神经免疫学
- 细胞和分子神经科学
- 炎症性疾病 炎症性疾病
背景情况:
- 实验性自身免疫脑膜炎 (EAE) 模型多发性硬化症,一种中枢神经系统 (CNS) 炎症性疾病.
- 穿越血脑屏障的白细胞透是EAE和多发性硬化症的关键病理事件.
- 了解白细胞粘附机制对于开发向疗法至关重要.
研究的目的:
- 在EAE中识别特定的粘附受体,调解白细胞附着到炎症的大脑内皮.
- 调查α4β1整蛋白在EAE期间白细胞进入中枢神经系统中的作用.
主要方法:
- 在体外粘附测试使用炎症EAE脑组织段.
- 测试抗体对各种粘附受体的抑制作用,包括α4β1整合蛋白.
- 在体内研究以评估抗α4整合素治疗对白细胞积累和EAE发展的影响.
主要成果:
- 淋巴细胞和单细胞选择性地附着在炎症的EAE脑血管中.
- 对α4β1整体的抗体显著抑制了这种白细胞结合.
- 在体内给予抗α4整合素可以防止中枢神经系统白细胞透和EAE的发展.
结论:
- 在EAE中,α4β1整体蛋白是白细胞进入中枢神经系统的关键媒介.
- 向α4β1整合素是中枢神经系统炎症性疾病 (如多发性硬化症) 的有前途的治疗策略.
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