| Matrilysin (Matrix Metalloproteinase-7) regulates anti-inflammatory and antifibrotic pulmonary dendritic cells that express CD103 (alpha(E)beta(7)-integrin). | |
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MedLine Citation:
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PMID: 19893044 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The E-cadherin receptor CD103 (alpha(E)beta(7)-integrin) is expressed on specific populations of pulmonary dendritic cells (DC) and T cells. However, CD103 function in the lung is not well understood. Matrilysin (MMP-7) expression is increased in lung injury and cleaves E-cadherin from injured lung epithelium. Thus, to assess matrilysin effects on CD103-E-cadherin interactions in lung injury, wild-type, CD103(-/-), and Mmp7(-/-) mice, in which E-cadherin isn't cleaved in the lung, were treated with bleomycin or bleomycin with nFMLP to reverse the defect in acute neutrophil influx seen in Mmp7(-/-) mice. Pulmonary CD103(+) DC were significantly increased in injured wild-type compared with Mmp7(-/-) mice, and CD103(+) leukocytes showed significantly enhanced interaction with E-cadherin on injured wild-type epithelium than with Mmp7(-/-) epithelium in vitro and in vivo. Bleomycin-treated CD103(-/-) mice had persistent neutrophilic inflammation, increased fibrosis, and increased mortality compared with wild-type mice, a phenotype that was partially recapitulated in bleomycin/nFMLP-treated Mmp7(-/-) mice. Soluble E-cadherin increased IL-12 and IL-10 and reduced IL-6 mRNA expression in wild-type bone marrow-derived DC but not in CD103(-/-) bone marrow-derived DC. Similar mRNA patterns were seen in lungs of bleomycin-injured wild-type, but not CD103(-/-) or Mmp7(-/-), mice. In conclusion, matrilysin regulates pulmonary localization of DC that express CD103, and E-cadherin cleavage may activate CD103(+) DC to limit inflammation and inhibit fibrosis. |
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Authors:
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Anne M Manicone; Isham Huizar; John K McGuire |
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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: 2009-11-05 |
Journal Detail:
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Title: The American journal of pathology Volume: 175 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-07 Completed Date: 2010-02-25 Revised Date: 2011-03-03 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 2319-31 Citation Subset: AIM; IM |
Affiliation:
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Center for Lung Biology, University of Washington, Seattle, Washington 98109, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD / biosynthesis Blotting, Western Cadherins / immunology, metabolism Dendritic Cells / immunology, metabolism* Flow Cytometry Immunohistochemistry Integrin alpha Chains / biosynthesis Lung Injury / immunology, metabolism* Matrix Metalloproteinase 7 / metabolism* Mice Mice, Inbred C57BL Mice, Knockout Neutrophil Infiltration Pneumonia / immunology, metabolism* Pulmonary Fibrosis / immunology, metabolism* Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
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HL02959/HL/NHLBI NIH HHS; HL068780/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Cadherins; 0/Integrin alpha Chains; 0/alpha E integrins; EC 3.4.24.23/Matrix Metalloproteinase 7 |
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