Focal MMP-2 and MMP-9 Activity at the Blood-Brain Barrier Promotes Chemokine-Induced Leukocyte Migration
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 immigr...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-02-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715000625 |
| _version_ | 1818932011024252928 |
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| author | Jian Song Chuan Wu Eva Korpos Xueli Zhang Smriti M. Agrawal Ying Wang Cornelius Faber Michael Schäfers Heinrich Körner Ghislain Opdenakker Rupert Hallmann Lydia Sorokin |
| author_facet | Jian Song Chuan Wu Eva Korpos Xueli Zhang Smriti M. Agrawal Ying Wang Cornelius Faber Michael Schäfers Heinrich Körner Ghislain Opdenakker Rupert Hallmann Lydia Sorokin |
| author_sort | Jian Song |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T04:25:42Z |
| format | Article |
| id | doaj.art-48551eaec71d41b1a20a5ae77bda7ac9 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T04:25:42Z |
| publishDate | 2015-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-48551eaec71d41b1a20a5ae77bda7ac92022-12-21T19:53:31ZengElsevierCell Reports2211-12472015-02-011071040105410.1016/j.celrep.2015.01.037Focal MMP-2 and MMP-9 Activity at the Blood-Brain Barrier Promotes Chemokine-Induced Leukocyte MigrationJian Song0Chuan Wu1Eva Korpos2Xueli Zhang3Smriti M. Agrawal4Ying Wang5Cornelius Faber6Michael Schäfers7Heinrich Körner8Ghislain Opdenakker9Rupert Hallmann10Lydia Sorokin11Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyDepartment of Clinical Radiology, University of Muenster, 48149 Muenster, GermanyEuropean Institute for Molecular Imaging, University of Muenster, 48149 Muenster, GermanyMenzies Institute for Medical Research, Hobart, TAS 7000, AustraliaDepartment of Microbiology and Immunobiology, Rega Institute for Medical Research, University of Leuven, 3000 Leuven, BelgiumInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, GermanyAlthough 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.http://www.sciencedirect.com/science/article/pii/S2211124715000625 |
| spellingShingle | Jian Song Chuan Wu Eva Korpos Xueli Zhang Smriti M. Agrawal Ying Wang Cornelius Faber Michael Schäfers Heinrich Körner Ghislain Opdenakker Rupert Hallmann Lydia Sorokin Focal MMP-2 and MMP-9 Activity at the Blood-Brain Barrier Promotes Chemokine-Induced Leukocyte Migration Cell Reports |
| title | Focal MMP-2 and MMP-9 Activity at the Blood-Brain Barrier Promotes Chemokine-Induced Leukocyte Migration |
| title_full | Focal MMP-2 and MMP-9 Activity at the Blood-Brain Barrier Promotes Chemokine-Induced Leukocyte Migration |
| title_fullStr | Focal MMP-2 and MMP-9 Activity at the Blood-Brain Barrier Promotes Chemokine-Induced Leukocyte Migration |
| title_full_unstemmed | Focal MMP-2 and MMP-9 Activity at the Blood-Brain Barrier Promotes Chemokine-Induced Leukocyte Migration |
| title_short | Focal MMP-2 and MMP-9 Activity at the Blood-Brain Barrier Promotes Chemokine-Induced Leukocyte Migration |
| title_sort | focal mmp 2 and mmp 9 activity at the blood brain barrier promotes chemokine induced leukocyte migration |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715000625 |
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