Document Detail


Matrilysin (Matrix Metalloproteinase-7) regulates anti-inflammatory and antifibrotic pulmonary dendritic cells that express CD103 (alpha(E)beta(7)-integrin).
MedLine Citation:
PMID:  19893044     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Anne M Manicone; Isham Huizar; John K McGuire
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-11-05
Journal Detail:
Title:  The American journal of pathology     Volume:  175     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-07     Completed Date:  2010-02-25     Revised Date:  2011-03-03    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2319-31     Citation Subset:  AIM; IM    
Affiliation:
Center for Lung Biology, University of Washington, Seattle, Washington 98109, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
HL02959/HL/NHLBI NIH HHS; HL068780/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Cadherins; 0/Integrin alpha Chains; 0/alpha E integrins; EC 3.4.24.23/Matrix Metalloproteinase 7

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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