Cell reports (Cambridge), 2015-02, Vol.10 (7), p.1040-1054
2015
Details
- Autor(en) / Beteiligte
- Titel
- Focal MMP-2 and MMP-9 Activity at the Blood-Brain Barrier Promotes Chemokine-Induced Leukocyte Migration
- Ist Teil von
- Cell reports (Cambridge), 2015-02, Vol.10 (7), p.1040-1054
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2015
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. [Display omitted] •MMP-2 and MMP-9 activity occurs at the blood-brain barrier•Cytokines derived from infiltrating leukocytes control MMP activity at the BBB•MMPs modulate chemokines at the BBB required for leukocyte chemotaxis•Cytokines, chemokines, and MMPs act together to accelerate leukocyte chemotaxis Chemokines are required for leukocyte migration into the CNS; however, additional MMP-2/9 activity specifically at the border of the CNS parenchyma strongly enhances this transmigration process. Song et al. show that cytokines derived from infiltrating leukocytes regulate MMP-2/9 activity at the parenchymal border, which differentially modulates chemokine activities, thereby accelerating leukocyte migration into the CNS.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2211-1247eISSN: 2211-1247DOI: 10.1016/j.celrep.2015.01.037Titel-ID: cdi_doaj_primary_oai_doaj_org_article_48551eaec71d41b1a20a5ae77bda7ac9
- Format
- –
- Schlagworte
- Animals, Astrocytes - cytology, Astrocytes - drug effects, Astrocytes - metabolism, Blood-Brain Barrier - metabolism, Cell Movement - drug effects, Cells, Cultured, Central Nervous System - metabolism, Chemokines - metabolism, Encephalomyelitis, Autoimmune, Experimental - metabolism, Encephalomyelitis, Autoimmune, Experimental - pathology, Interferon-gamma - pharmacology, Interleukin-17 - pharmacology, Leukocytes - cytology, Leukocytes - metabolism, Matrix Metalloproteinase 2 - deficiency, Matrix Metalloproteinase 2 - genetics, Matrix Metalloproteinase 2 - metabolism, Matrix Metalloproteinase 9 - deficiency, Matrix Metalloproteinase 9 - genetics, Matrix Metalloproteinase 9 - metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Signal Transduction - drug effects, T-Lymphocytes - immunology, T-Lymphocytes - metabolism, Tumor Necrosis Factor-alpha - pharmacology