Reinke Emily K, Lee Jangeun, Zozulya Alla, Karman Jozsef, Muller William A, Sandor Matyas, Fabry Zsuzsanna
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
J Neuroimmunol. 2007 May;186(1-2):86-93. doi: 10.1016/j.jneuroim.2007.03.014. Epub 2007 Apr 27.
The homophilic cell adhesion molecule PECAM-1 is a major participant in the migration of leukocytes across endothelium. We examined the ability of a chimeric soluble PECAM-1 fused to human IgG-Fc to impair leukocyte entry through the blood-brain barrier and reduce CNS autoimmunity. sPECAM-Fc impaired migration of lymphocytes across brain endothelial monolayers and diminished the severity of EAE, an experimental model of MS, when administered at the onset of symptoms. However, in mice transgenic for sPECAM-Fc, the chronically elevated levels of sPECAM-Fc hastened onset of EAE disease without significantly changing clinical score severity. Our data suggest that short-term treatment of diseases like MS with sPECAM-Fc has therapeutic potential.
同嗜性细胞黏附分子PECAM-1是白细胞穿越内皮迁移的主要参与者。我们检测了与人IgG-Fc融合的嵌合可溶性PECAM-1损害白细胞通过血脑屏障进入并降低中枢神经系统自身免疫的能力。当在症状发作时给药,sPECAM-Fc损害淋巴细胞穿越脑内皮单层的迁移,并减轻了EAE(一种多发性硬化症的实验模型)的严重程度。然而,在转sPECAM-Fc基因的小鼠中,sPECAM-Fc的长期高水平加速了EAE疾病的发作,而没有显著改变临床评分的严重程度。我们的数据表明,用sPECAM-Fc对多发性硬化症等疾病进行短期治疗具有治疗潜力。