Selmaj K, Walczak A, Mycko M, Berkowicz T, Kohno T, Raine C S
Department of Neurology, Medical Academy of Lodz, Poland.
Eur J Immunol. 1998 Jun;28(6):2035-44. doi: 10.1002/(SICI)1521-4141(199806)28:06<2035::AID-IMMU2035>3.0.CO;2-A.
The effect of a novel TNF binding protein (TNFbp), a polyethylene glycol-linked form of the type I soluble receptor of TNF, on the expression of adhesion molecules has been investigated with a passive transfer model of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. The expression of L-selectin, VLA-4 and LFA-1 on spleen cells of EAE animals treated with TNFbp or saline was examined by FACS analysis. The expression of VCAM-1 and ICAM-1 was investigated by immunochemistry in spinal cord tissue of SJL/J mice with EAE. In animals sensitized for EAE and treated with TNFbp, the expression of VCAM-1 in the central nervous system as well as VLA-4 on spleen cells was clearly diminished. Reduction in VCAM-1 staining and VLA-4 expression corresponded to inhibition of inflammation in the spinal cord and to prevention of clinical signs of EAE. The results have also shown that myelin basic protein responses as well as non-antigen-specific responses were not diminished in animals treated with TNFbp. The findings suggest that TNFbp might prevent EAE development by modulating the expression of VCAM-1 and VLA-4.
一种新型肿瘤坏死因子结合蛋白（TNFbp），即肿瘤坏死因子I型可溶性受体的聚乙二醇连接形式，对粘附分子表达的影响已通过SJL/J小鼠实验性自身免疫性脑脊髓炎（EAE）的被动转移模型进行了研究。通过流式细胞术分析检测了用TNFbp或生理盐水处理的EAE动物脾细胞上L-选择素、VLA-4和LFA-1的表达。通过免疫化学方法研究了患有EAE的SJL/J小鼠脊髓组织中VCAM-1和ICAM-1的表达。在对EAE致敏并接受TNFbp治疗的动物中，中枢神经系统中VCAM-1的表达以及脾细胞上VLA-4的表达明显减少。VCAM-1染色和VLA-4表达的降低与脊髓炎症的抑制以及EAE临床症状的预防相对应。结果还表明，在用TNFbp治疗的动物中，髓鞘碱性蛋白反应以及非抗原特异性反应并未减弱。这些发现表明，TNFbp可能通过调节VCAM-1和VLA-4的表达来预防EAE的发展。
