Document Detail


S100A10 regulates plasminogen-dependent macrophage invasion.
MedLine Citation:
PMID:  20424186     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The plasminogen activation system plays an integral role in the migration of macrophages in response to an inflammatory stimulus, and the binding of plasminogen to its cell-surface receptor initiates this process. Although previous studies from our laboratory have shown the importance of the plasminogen receptor S100A10 in cancer cell plasmin production, the potential role of this protein in macrophage migration has not been investigated. Using thioglycollate to induce a peritoneal inflammatory response, we demonstrate, for the first time, that compared with wild-type (WT) mice, macrophage migration across the peritoneal membrane into the peritoneal cavity in S100A10-deficient (S100A10(-/-)) mice was decreased by up to 53% at 24, 48, and 72 hours. Furthermore, the number of S100A10-deficient macrophages that infiltrated Matrigel plugs was reduced by 8-fold compared with their WT counterpart in vivo. Compared with WT macrophages, macrophages from S100A10(-/-) mice demonstrated a 50% reduction in plasmin-dependent invasion across a Matrigel barrier and a 45% reduction in plasmin generation in vitro. This loss in plasmin-dependent invasion was in part the result of a decreased generation of plasmin and a decreased activation of pro-MMP-9 by S100A10-deficient macrophages. This study establishes a direct involvement of S100A10 in macrophage recruitment in response to inflammatory stimuli.
Authors:
Paul A O'Connell; Alexi P Surette; Robert S Liwski; Per Svenningsson; David M Waisman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-27
Journal Detail:
Title:  Blood     Volume:  116     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-20     Completed Date:  2010-09-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1136-46     Citation Subset:  AIM; IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Annexin A2 / physiology*
Apoptosis
Blotting, Western
Cell Adhesion
Cell Movement
Cell Proliferation
Collagen / metabolism
Drug Combinations
Female
Fibrinolysin / metabolism
Flow Cytometry
Immunoenzyme Techniques
Inflammation / chemically induced,  metabolism,  pathology*
Laminin / metabolism
Macrophages, Peritoneal / metabolism*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Plasminogen / metabolism*
Proteoglycans / metabolism
S100 Proteins / physiology*
Thioglycolates / toxicity
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Annexin A2; 0/Drug Combinations; 0/Laminin; 0/Proteoglycans; 0/S100 Proteins; 0/S100 calcium binding protein A10; 0/Thioglycolates; 119978-18-6/matrigel; 9001-91-6/Plasminogen; 9007-34-5/Collagen; EC 3.4.21.7/Fibrinolysin
Comments/Corrections
Comment In:
Blood. 2010 Aug 19;116(7):1022-4   [PMID:  20724548 ]

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


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