title: MCP-1 induces migration of adult neural stem cells.
abstract: As a model for brain inflammation we previously studied transcriptional profiles of tumor necrosis factor-alpha (TNF)treated U373 astroglioma cells. In previous work we were able to demonstrate that the chemokine monocyte chemoattractant protein-1 (MCP-1, SCYA2, CCL2, MCAF) expression in U373 cells was inducible by TNF-alpha treatment. Demonstrably MCP-1 mRNA and protein expression in U373 cells was sustainable over time and at the highest level of all genes analyzed (Schwamborn et al., BMC Genomics 4, 46, 2003). In the hematopoietic system MCP-1 is a CC chemokine that attracts monocytes, memory T lymphocytes, and natural killer cells. In search of further functions in brain inflammation we tested the hypothesis that MCP-1 acts as a chemokine on neural stem cells. Here we report that MCP-1 activates the migration capacity of rat-derived neural stem cells. The migration of stem cells in a Boyden chamber analysis was elevated after stimulation with MCP-1. Time-lapse video microscopy visualized the migration of single stem cells from neurospheres in MCP-1-treated cultures, whereas untreated cultures depicted no migration at all, but showed signs of sprouting. Expression of the MCP-1 receptor CCR2 in neurosphere cultures was verified by RT-PCR and immunofluorescence microscopy. Supernatants from TNF-treated U373 cells also induced migration of neural stem cells.
authors.affiliation: Institut für Neurobiochemie, Universität Witten/Herdecke, Witten, Germany.
authors.forename: Darius
authors.initials: D
authors.lastname: Widera
authors.forename: Wolf
authors.initials: W
authors.lastname: Holtkamp
authors.forename: Frank
authors.initials: F
authors.lastname: Entschladen
authors.forename: Bernd
authors.initials: B
authors.lastname: Niggemann
authors.forename: Kurt
authors.initials: K
authors.lastname: Zänker
authors.forename: Barbara
authors.initials: B
authors.lastname: Kaltschmidt
authors.forename: Christian
authors.initials: C
authors.lastname: Kaltschmidt
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000473:pathology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology; D007694:Killer Cells, Natural / Q000502:physiology; D020547:Lateral Ventricles / Q000166:cytology / Q000502:physiology*; D051381:Rats; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C515334:CCR2 protein, human; C515336:Ccr2 protein, rat; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha