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


Song, J and Wu, C and Korpos, E and Zhang, X and Agrawal, SM and Wang, Y and Faber, C and Schafers, M and Korner, H and Opdenakker, G and Hallmann, R and Sorokin, L, Focal MMP-2 and MMP-9 activity at the blood-brain barrier promotes chemokine-induced leukocyte migration, Cell Reports, 10, (7) pp. 1040-1054. ISSN 2211-1247 (2015) [Refereed Article]


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Licensed under Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0)

DOI: doi:10.1016/j.celrep.2015.01.037


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.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Immunology not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Korner, H (Professor Heinrich Korner)
ID Code:98852
Year Published:2015
Web of Science® Times Cited:119
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-03-04
Last Modified:2017-11-06
Downloads:304 View Download Statistics

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