| Expression of the HGF receptor c-met by macrophages in experimental autoimmune encephalomyelitis. | |
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MedLine Citation:
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PMID: 19941340 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hepatocyte growth factor (HGF) is a pleiotropic cytokine able to evoke a wide array of cellular responses including proliferation, migration, and survival through activation of its receptor c-met. Various types of leukocytes have been described to express c-met suggesting that HGF/c-met signaling may directly influence leukocyte responses in inflammation. We have investigated the HGF/c-met pathway in experimental autoimmune encephalomyelitis (EAE), a common mouse model of multiple sclerosis (MS), in which macrophages play a dual role, contributing directly to CNS damage at disease onset but promoting recovery during remission by removing myelin debris. Here we show that during EAE both HGF and c-met are expressed in the CNS and that c-met is activated. We subsequently demonstrate that c-met is primarily expressed in inflammatory lesions by macrophages and a small number of dendritic cells (DCs) and oligodendrocyte progenitor cells (OPCs) but not by microglia or T cells. Complementary in vitro experiments show that only LPS and TNFalpha, but not IL-6, IL-10, or IL-13, are able to induce c-met expression in macrophages. In addition, using TNF signaling deficient macrophages we demonstrate that LPS and TNFalpha induce c-met through distinct pathways. Furthermore, TNFalpha- and LPS-induced c-met is functional because treatment of macrophages with recombinant HGF results in rapid phosphorylation of c-met. Interestingly, HGF/c-met signaling does not modulate cytokine expression, phagocytosis, or antigen presentation but promotes proliferation of activated macrophages. Taken together, our data indicate a pro-inflammatory role for the HGF/c-met pathway in EAE rather than a role in the initiation of repair mechanisms. |
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Authors:
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Martijn Moransard; Mandy Sawitzky; Adriano Fontana; Tobias Suter |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Glia Volume: 58 ISSN: 1098-1136 ISO Abbreviation: Glia Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-02-11 Completed Date: 2010-04-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8806785 Medline TA: Glia Country: United States |
Other Details:
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Languages: eng Pagination: 559-71 Citation Subset: IM |
Affiliation:
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Division of Clinical Immunology, University Hospital Zurich, Moussonstrasse 13, CH-8044 Z?rich, Switzerland. martijn.moransard@usz.ch |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD / metabolism Bone Marrow Cells Cell Proliferation / drug effects Cells, Cultured Central Nervous System / pathology* Cytokines / genetics, metabolism Dendritic Cells / drug effects, metabolism Disease Models, Animal Encephalomyelitis, Autoimmune, Experimental / chemically induced, pathology* Female Flow Cytometry Gene Expression Regulation / drug effects, physiology* Glycoproteins Hepatocyte Growth Factor / genetics, metabolism, pharmacology Lipopolysaccharides / pharmacology Macrophages / metabolism* Mice Mice, Inbred C57BL Mice, Knockout Microglia / physiology Nitrates / metabolism Oligodendroglia / physiology Peptide Fragments Phagocytosis / physiology Proto-Oncogene Proteins c-met / genetics, metabolism* Stem Cells Time Factors Tumor Necrosis Factor-alpha / deficiency |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Cytokines; 0/Glycoproteins; 0/Lipopolysaccharides; 0/Nitrates; 0/Peptide Fragments; 0/Tumor Necrosis Factor-alpha; 0/myelin oligodendrocyte glycoprotein (35-55); 67256-21-7/Hepatocyte Growth Factor; EC 2.7.10.1/Proto-Oncogene Proteins c-met |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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