title: Regulation of macrophage migration by a novel plasminogen receptor Plg-R KT.
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.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, 10550 N Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Lighvani
authors.forename: Nagyung
authors.initials: N
authors.lastname: Baik
authors.forename: Jenna E
authors.initials: JE
authors.lastname: Diggs
authors.forename: Sophia
authors.initials: S
authors.lastname: Khaldoyanidi
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Parmer
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Miles
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001672:Biocompatible Materials; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D003094:Collagen; D004195:Disease Models, Animal; D004338:Drug Combinations; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007797:Laminin; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010538:Peritonitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D010958:Plasminogen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011509:Proteoglycans; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000276:immunology / Q000378:metabolism; D013864:Thioglycolates / Q000633:toxicity
chemical_list: D000911:Antibodies, Monoclonal; D001672:Biocompatible Materials; D004338:Drug Combinations; D007797:Laminin; C569300:PLG-R(KT) protein, mouse; C548063:PLGRKT protein, human; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D013864:Thioglycolates; C059485:matrigel; D010958:Plasminogen; D003094:Collagen; D005341:Fibrinolysin; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse