title: Focal MMP-2 and MMP-9 activity at the blood-brain barrier promotes chemokine-induced leukocyte migration.
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.
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany.
authors.forename: Chuan
authors.initials: C
authors.lastname: Wu
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Korpos
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
authors.forename: Xueli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany.
authors.forename: Smriti M
authors.initials: SM
authors.lastname: Agrawal
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Clinical Radiology, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Faber
authors.affiliation: European Institute for Molecular Imaging, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
authors.affiliation: Menzies Institute for Medical Research, Hobart, TAS 7000, Australia.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Körner
authors.affiliation: Department of Microbiology and Immunobiology, Rega Institute for Medical Research, University of Leuven, 3000 Leuven, Belgium.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Hallmann
authors.affiliation: Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany; Cells-in-Motion Cluster of Excellence, University of Muenster, 48149 Muenster, Germany. Electronic address: sorokin@uni-muenster.de.
authors.forename: Lydia
authors.initials: L
authors.lastname: Sorokin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology; D020381:Interleukin-17 / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018925:Chemokines; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9