Dendritic Cell Transmigration through Brain Microvessel Endothelium Is Regulated by MIP-1α Chemokine and Matrix Metalloproteinases1
Dendritic Cell Transmigration through Brain Microvessel Endothelium Is Regulated by MIP-1α Chemokine and Matrix Metalloproteinases1
复制标题
MIP-1α 趋化因子和基质金属蛋白酶调节树突状细胞通过脑微血管内皮的迁移1
作者：
A. Zozulya;E. Reinke;D. Baiu;J. Karman;M. Sandor;Z. Fabry
炎症性疾病期间，树突状细胞(DC)在中枢神经系统内聚集，但调节其进入中枢神经系统的确切机制尚不清楚。我们现在报道，MIP-1α增加了骨髓来源的绿色荧光蛋白标记的树突状细胞跨脑微血管内皮细胞单层的迁移。此外，当DC跨脑毛细血管内皮细胞单层迁移时，内皮紧密连接的重要元件occludin被重组，而不会引起跨内皮细胞电阻测量的屏障完整性的显著变化。我们发现DC产生基质金属蛋白酶-2和-9，而基质金属蛋白酶抑制剂GM6001可减少基线和MIP-1α诱导的DC迁移。这些观察结果表明，DC跨脑内皮细胞单层的迁移部分依赖于基质金属蛋白酶。迁移的DC表达较高水平的CD40、CD80和CD86共刺激分子，并诱导T细胞增殖，提示DC跨脑内皮细胞单层迁移有助于维持DC的抗原提呈功能。基质金属蛋白酶依赖于树突状细胞在脑内皮细胞单层的迁移，增加了基质金属蛋白酶阻滞剂可以减少中枢神经系统T细胞募集和神经炎症的可能性。
Dendritic cells (DCs) accumulate in the CNS during inflammatory diseases, but the exact mechanism regulating their traffic into the CNS remains to be defined. We now report that MIP-1α increases the transmigration of bone marrow-derived, GFP-labeled DCs across brain microvessel endothelial cell monolayers. Furthermore, occludin, an important element of endothelial tight junctions, is reorganized when DCs migrate across brain capillary endothelial cell monolayers without causing significant changes in the barrier integrity as measured by transendothelial electrical resistance. We show that DCs produce matrix metalloproteinases (MMP) -2 and -9 and GM6001, an MMP inhibitor, decreases both baseline and MIP-1α-induced DC transmigration. These observations suggest that DC transmigration across brain endothelial cell monolayers is partly MMP dependent. The migrated DCs express higher levels of CD40, CD80, and CD86 costimulatory molecules and induce T cell proliferation, indicating that the transmigration of DCs across brain endothelial cell monolayers contributes to the maintenance of DC Ag-presenting function. The MMP dependence of DC migration across brain endothelial cell monolayers raises the possibility that MMP blockers may decrease the initiation of T cell recruitment and neuroinflammation in the CNS.
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影响因子：
4
作者：
C. M. Itallie;James M. Anderson
通讯作者：
C. M. Itallie;James M. Anderson
DOI：
10.1172/jci21087
发表时间：
2004-04
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
G. Sitia;M. Isogawa;M. Iannacone;I. Campbell;F. Chisari;L. Guidotti
通讯作者：
G. Sitia;M. Isogawa;M. Iannacone;I. Campbell;F. Chisari;L. Guidotti
影响因子：
32.4
作者：
Randolph, GJ;Inaba, K;Muller, WA
通讯作者：
Muller, WA
DOI：
10.1165/rcmb.2003-0370oc
发表时间：
2004-06-01
影响因子：
6.4
作者：
Ichiyasu, H;McCormack, JM;Schneeberger, EE
通讯作者：
Schneeberger, EE
小鼠过继转移的慢性复发性实验性自身免疫性脑脊髓炎。
DOI：
--
发表时间：
1984
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
Raine,CS;Mokhtarian,F;McFarlin,DE
通讯作者：
McFarlin,DE