血脑屏障处局部的基质金属蛋白酶-2和基质金属蛋白酶-9活性促进趋化因子诱导的白细胞迁移。

Focal MMP-2 and MMP-9 activity at the blood-brain barrier promotes chemokine-induced leukocyte migration.

作者信息

Song Jian, Wu Chuan, Korpos Eva, Zhang Xueli, Agrawal Smriti M, Wang Ying, Faber Cornelius, Schäfers Michael, Körner Heinrich, Opdenakker Ghislain, Hallmann Rupert, Sorokin Lydia

机构信息

Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.

Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany.

出版信息

Cell Rep. 2015 Feb 24;10(7):1040-54. doi: 10.1016/j.celrep.2015.01.037. Epub 2015 Feb 19.

DOI:10.1016/j.celrep.2015.01.037

PMID:25704809

Abstract

Although chemokines are sufficient for chemotaxis of various cells, increasing evidence exists for their fine-tuning by selective proteolytic processing. Using a model of immune cell chemotaxis into the CNS (experimental autoimmune encephalomyelitis [EAE]) that permits precise localization of immigrating leukocytes at the blood-brain barrier, we show that, whereas chemokines are required for leukocyte migration into the CNS, additional MMP-2/9 activities specifically at the border of the CNS parenchyma strongly enhance this transmigration process. Cytokines derived from infiltrating leukocytes regulate MMP-2/9 activity at the parenchymal border, which in turn promotes astrocyte secretion of chemokines and differentially modulates the activity of different chemokines at the CNS border, thereby promoting leukocyte migration out of the cuff. Hence, cytokines, chemokines, and cytokine-induced MMP-2/9 activity specifically at the inflammatory border collectively act to accelerate leukocyte chemotaxis across the parenchymal border.

摘要

尽管趋化因子足以介导各种细胞的趋化作用，但越来越多的证据表明，它们可通过选择性蛋白水解加工进行微调。利用免疫细胞向中枢神经系统趋化的模型（实验性自身免疫性脑脊髓炎 [EAE]），该模型可精确确定迁移的白细胞在血脑屏障处的位置，我们发现，虽然趋化因子是白细胞迁移到中枢神经系统所必需的，但特别是在中枢神经系统实质边界处的额外基质金属蛋白酶-2/9（MMP-2/9）活性会强烈增强这种迁移过程。浸润白细胞衍生的细胞因子调节实质边界处的MMP-2/9活性，这反过来又促进星形胶质细胞分泌趋化因子，并差异性地调节中枢神经系统边界处不同趋化因子的活性，从而促进白细胞从袖套中迁移出来。因此，细胞因子、趋化因子以及特别是在炎症边界处由细胞因子诱导的MMP-2/9活性共同作用，加速白细胞穿过实质边界的趋化作用。