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Regulation of macrophage migration by a novel plasminogen receptor Plg-R(KT)

Academic Article
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Overview

authors

  • Lighvani, S.
  • Baik, N.
  • Diggs, J. E.
  • Khaldoyanidi, S.
  • Parmer, R. J.
  • Miles, Lindsey

publication date

  • November 2011

journal

  • Blood  Journal

abstract

  • 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. In the present study, 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 urokinase-type plasminogen activator (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 with 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. We conclude that Plg-R(KT) plays a key role in the plasminogen-dependent regulation of macrophage invasion, chemotactic migration, and recruitment in the inflammatory response.

subject areas

  • Animals
  • Antibodies, Monoclonal
  • Biocompatible Materials
  • Cell Movement
  • Collagen
  • Disease Models, Animal
  • Drug Combinations
  • Female
  • Fibrinolysin
  • Humans
  • Laminin
  • Macrophages
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Monocytes
  • Peritonitis
  • Plasminogen
  • Proteoglycans
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Thioglycolates
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Identity

PubMed Central ID

  • PMC3217361

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2011-03-344242

PubMed ID

  • 21940822
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Additional Document Info

start page

  • 5622

end page

  • 5630

volume

  • 118

issue

  • 20

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