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- Shahrzad Lighvani
- Department of Cell Biology, The Scripps Research Institute, La Jolla, CA;
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- Nagyung Baik
- Department of Cell Biology, The Scripps Research Institute, La Jolla, CA;
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- Jenna E. Diggs
- Department of Cell Biology, The Scripps Research Institute, La Jolla, CA;
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- Sophia Khaldoyanidi
- Department of Regenerative Medicine, Torrey Pines Institute for Molecular Studies, La Jolla, CA;
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- Robert J. Parmer
- Department of Medicine, University of California San Diego, La Jolla, CA; and
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- Lindsey A. Miles
- Department of Cell Biology, The Scripps Research Institute, La Jolla, CA;
抄録
<jats:title>Abstract</jats:title><jats:p>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-RKT, which exposes a C-terminal lysine on the cell surface. In the present study, we investigated the role of Plg-RKT in macrophage invasion, chemotactic migration, and recruitment. Plg-RKT was prominently expressed in membranes of human peripheral blood monocytes and monocytoid cells. Plasminogen activation by urokinase-type plasminogen activator (uPA) was markedly inhibited (by 39%) by treatment with anti–Plg-RKT mAb. Treatment of monocytes with anti–Plg-RKT mAb substantially inhibited invasion through the representative matrix, Matrigel, in response to MCP-1 (by 54% compared with isotype control). Furthermore, chemotactic migration was also inhibited by treatment with anti–Plg-RKT mAb (by 64%). In a mouse model of thioglycollate-induced peritonitis, anti–Plg-RKT mAb markedly inhibited macrophage recruitment (by 58%), concomitant with a reduction in pro–MMP-9 activation in the inflamed peritoneum. Treatment with anti–Plg-RKT mAb did not further reduce the low level of macrophage recruitment in plasminogen-null mice. We conclude that Plg-RKT plays a key role in the plasminogen-dependent regulation of macrophage invasion, chemotactic migration, and recruitment in the inflammatory response.</jats:p>
収録刊行物
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- Blood
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Blood 118 (20), 5622-5630, 2011-11-17
American Society of Hematology