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The novel plasminogen receptor, Plg-RKT, regulates macrophage migration.
MedLine Citation:
PMID:  21940822     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Localization of plasmin on macrophages and activation of pro-MMP-9 play key roles in macrophage recruitment in the inflammatory response. These functions are promoted by plasminogen receptors exposing C-terminal basic residues on the macrophage surface. Recently, we identified a novel transmembrane plasminogen receptor, Plg-R(KT), which exposes a C-terminal lysine on the cell surface. Here we investigated the role of Plg-R(KT) in macrophage invasion, chemotactic migration and recruitment. Plg-R(KT) was prominently expressed in membranes of human peripheral blood monocytes and monocytoid cells. Plasminogen activation by uPA was markedly inhibited (by 39 %) by treatment with anti-Plg-R(KT) mAb. Treatment of monocytes with anti-Plg-R(KT) mAb substantially inhibited invasion through the representative matrix, Matrigel, in response to MCP-1 (by 54 % compared to isotype control). Furthermore, chemotactic migration was also inhibited by treatment with anti-Plg-R(KT) mAb (by 64%). In a mouse model of thioglycollate-induced peritonitis, anti-Plg-R(KT) mAb markedly inhibited macrophage recruitment (by 58%), concomitant with a reduction in pro-MMP-9 activation in the inflamed peritoneum. Treatment with anti-Plg-R(KT) mAb did not further reduce the low level of macrophage recruitment in plasminogen null mice. Thus, Plg-R(KT) plays a key role in plasminogen-dependent regulation of macrophage invasion, chemotactic migration and recruitment in the inflammatory response.
Authors:
Shahrzad Lighvani; Nagyung Baik; Jenna E Diggs; Sophia Khaldoyanidi; Robert J Parmer; Lindsey A Miles
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-22
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA, United States;
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