| First Author | Gong Y | Year | 2008 |
| Journal | J Clin Invest | Volume | 118 |
| Issue | 9 | Pages | 3012-24 |
| PubMed ID | 18677407 | Mgi Jnum | J:140977 |
| Mgi Id | MGI:3814981 | Doi | 10.1172/JCI32750 |
| Citation | Gong Y, et al. (2008) Inflammatory macrophage migration requires MMP-9 activation by plasminogen in mice. J Clin Invest 118(9):3012-24 |
| abstractText | Inflammation plays a critical role in the development of cardiovascular diseases. Infiltration of leukocytes to sites of injury requires their exit from the blood and migration across basement membrane; this process has been postulated to require remodeling of the ECM. Plasminogen (Plg) is a protease that binds to the ECM and, upon conversion to plasmin, degrades multiple ECM proteins. In addition, plasmin directly activates MMPs. Here, we used Plg(-/-) mice to investigate the role of Plg in inflammatory leukocyte migration. After induction of peritonitis by thioglycollate injection, we found that Plg(-/-) mice displayed diminished macrophage trans-ECM migration and decreased MMP-9 activation. Furthermore, injection of the active form of MMP-9 in Plg(-/-) mice rescued macrophage migration in this model. We used periaortic application of CaCl2 to induce abdominal aortic aneurysm (AAA) and found that Plg(-/-) mice displayed reduced macrophage infiltration and were protected from aneurysm formation. Administration of active MMP-9 to Plg(-/-) mice promoted macrophage infiltration and the development of AAA. These data suggest that Plg regulates macrophage migration in inflammation via activation of MMP-9, which, in turn, regulates the ability of the cells to migrate across ECM. Thus, targeting the Plg/MMP-9 pathway may be an attractive approach to regulate inflammatory responses and AAA development. |
