| First Author | Lighvani S | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 20 | Pages | 5622-30 |
| PubMed ID | 21940822 | Mgi Jnum | J:178885 |
| Mgi Id | MGI:5300451 | Doi | 10.1182/blood-2011-03-344242 |
| Citation | Lighvani S, et al. (2011) Regulation of macrophage migration by a novel plasminogen receptor Plg-R KT. Blood 118(20):5622-30 |
| abstractText | 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. |
