title: Interacting chemokine signals regulate dendritic cells in acute brain injury.
abstract: Brain trauma is known to activate inflammatory cells via various chemokine signals although their interactions remain to be characterized. Mice deficient in Ccl3, Ccr2 or Cxcl10 were compared with wildtype mice after controlled cortical impact injury. Expression of Ccl3 in wildtypes was rapidly upregulated in resident, regularly spaced reactive microglia. Ccl3-deficiency enhanced endothelial expression of platelet selectin and invasion of peripheral inflammatory cells. Appearance of Ccr2 transcripts, encoding the Ccl2 receptor, reflected invasion of lysozyme 2-expressing phagocytes and classical antigen-presenting dendritic cells expressing major histocompatibility complex class II. Ccr2 also directed clustered plasmacytoid dendritic cells positive for the T-cell attracting chemokine Cxcl10. A reduction in Ccr2 and dendritic cells was found in injured wildtype cortex after cyclophosphamide treatment resembling effects of Ccr2-deficiency. The findings demonstrate the feasibility to control inflammation in the injured brain by regulating chemokine-dependent pathways.
authors.affiliation: Department of Neuroscience, Developmental Neuroscience, Biomedical Center, Uppsala University, Uppsala, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Israelsson
authors.affiliation: Department of Neuroscience, Developmental Neuroscience, Biomedical Center, Uppsala University, Uppsala, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Kylberg
authors.affiliation: Department of Neuroscience, Developmental Neuroscience, Biomedical Center, Uppsala University, Uppsala, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Bengtsson
authors.affiliation: Department of Neuroscience, Neurosurgery, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Hillered
authors.affiliation: Department of Neuroscience, Developmental Neuroscience, Biomedical Center, Uppsala University, Uppsala, Sweden.
authors.forename: Ted
authors.initials: T
authors.lastname: Ebendal
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D003520:Cyclophosphamide / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D017353:Gene Deletion; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D010586:Phagocytes / Q000378:metabolism / Q000502:physiology; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C496534:Ccl3 protein, mouse; C515335:Ccr2 protein, mouse; D054405:Chemokine CCL3; D054357:Chemokine CXCL10; D018925:Chemokines; C485433:Cxcl10 protein, mouse; D054390:Receptors, CCR2; D003520:Cyclophosphamide