Targeting the tetraspanin CD81 blocks monocyte transmigration and ameliorates EAE

被引:32
作者
Dijkstra, S. [1 ,4 ]
Kooij, G. [1 ]
Verbeek, R. [4 ]
van der Pol, S. M. A. [1 ]
Amor, S. [2 ]
Geisert, E. E., Jr. [3 ]
Dijkstra, C. D. [1 ]
van Noort, J. M. [4 ]
de Vries, H. E. [1 ]
机构
[1] Vrije Univ Amsterdam Med Ctr, Dept Mol Cell Biol & Immunol, NL-1007 MB Amsterdam, Netherlands
[2] Vrije Univ Amsterdam Med Ctr, Dept Pathol, NL-1007 MB Amsterdam, Netherlands
[3] Univ Tennessee, Ctr Hlth Sci, Dept Ophthalmol, Memphis, TN 38163 USA
[4] TNO Qual Life, Dept Biosci, Leiden, Netherlands
关键词
tetraspanins; CD81; multiple sclerosis; transendothelial migration; therapeutic antibodies; EAE;
D O I
10.1016/j.nbd.2008.05.018
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Leukocyte infiltration is a key step in the development of demyelinating lesions in multiple sclerosis (MS), and molecules mediating leukocyte-endothelial interactions represent prime candidates for the development of therapeutic strategies. Here we studied the effects of blocking the integrin-associated tetraspanin CD81 in in vitro and in vivo models for MS. In an in vitro setting mAb against CD81 significantly reduced monocyte transmigration across brain endothelial cell monolayers, both in rodent and human models. Interestingly, leukocyte as well as endothelial CD81 was involved in this inhibitory effect. To assess their therapeutic potential, CD81 mAb were administered to mice suffering from experimental autoimmune encephalomyelitis (EAE). We found that Eat2, but not 2F7 mAb directed against mouse CD81 significantly reduced the development of neurological symptoms of EAE when using a preventive approach. Concomitantly, Eat2 treated animals showed reduced inflammation in the spinal cord. We conclude that CD81 represents a potential therapeutic target to interfere with leukocyte infiltration and ameliorate inflammatory neurological damage in MS. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:413 / 421
页数:9
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