| The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques. | |
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MedLine Citation:
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PMID: 22231519 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Atherosclerotic plaque formation is fueled by the persistence of lipid-laden macrophages in the artery wall. The mechanisms by which these cells become trapped, thereby establishing chronic inflammation, remain unknown. Here we found that netrin-1, a neuroimmune guidance cue, was secreted by macrophages in human and mouse atheroma, where it inactivated the migration of macrophages toward chemokines linked to their egress from plaques. Acting via its receptor, UNC5b, netrin-1 inhibited the migration of macrophages directed by the chemokines CCL2 and CCL19, activation of the actin-remodeling GTPase Rac1 and actin polymerization. Targeted deletion of netrin-1 in macrophages resulted in much less atherosclerosis in mice deficient in the receptor for low-density lipoprotein and promoted the emigration of macrophages from plaques. Thus, netrin-1 promoted atherosclerosis by retaining macrophages in the artery wall. Our results establish a causative role for negative regulators of leukocyte migration in chronic inflammation. |
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Authors:
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Janine M van Gils; Merran C Derby; Luciana R Fernandes; Bhama Ramkhelawon; Tathagat D Ray; Katey J Rayner; Sajesh Parathath; Emilie Distel; Jessica L Feig; Jacqueline I Alvarez-Leite; Alistair J Rayner; Thomas O McDonald; Kevin D O'Brien; Lynda M Stuart; Edward A Fisher; Adam Lacy-Hulbert; Kathryn J Moore |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-01-08 |
Journal Detail:
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Title: Nature immunology Volume: 13 ISSN: 1529-2916 ISO Abbreviation: Nat. Immunol. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-01-20 Completed Date: 2012-03-08 Revised Date: 2012-03-15 |
Medline Journal Info:
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Nlm Unique ID: 100941354 Medline TA: Nat Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 136-43 Citation Subset: IM |
Affiliation:
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Marc and Ruti Bell Vascular Biology and Disease Program, Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, New York, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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metabolism Animals Atherosclerosis / immunology* Cell Movement / immunology* Cells, Cultured Chemokine CCL19 / metabolism Chemokine CCL2 / metabolism Chimera / metabolism Gene Deletion Humans Macrophages / immunology* Mice Nerve Growth Factors / genetics, metabolism* Neuropeptides / metabolism Plaque, Atherosclerotic / immunology* Polymerization Receptors, Cell Surface / metabolism Tumor Suppressor Proteins / genetics, metabolism* rac GTP-Binding Proteins / metabolism rac1 GTP-Binding Protein / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01HL084312/HL/NHLBI NIH HHS; U01-AI073871/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/CCL19 protein, human; 0/CCL2 protein, human; 0/Ccl19 protein, mouse; 0/Ccl2 protein, mouse; 0/Chemokine CCL19; 0/Chemokine CCL2; 0/Nerve Growth Factors; 0/Neuropeptides; 0/RAC1 protein, human; 0/Rac1 protein, mouse; 0/Receptors, Cell Surface; 0/Tumor Suppressor Proteins; 0/UNC5B protein, human; 0/netrin receptors; 158651-98-0/netrin-1; EC 3.6.5.2/rac GTP-Binding Proteins; EC 3.6.5.2/rac1 GTP-Binding Protein |
| Comments/Corrections | |
Comment In:
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Cell Metab. 2012 Feb 8;15(2):135-6
[PMID:
22326216
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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