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| Content Provider | PubMed Central |
|---|---|
| Author | Cao, Chunzhang Lawrence, Daniel A. Li, Yang Arnim, Christine A. F. Von Herz, Joachim Su, Enming J. Makarova, Alexandra Hyman, Bradley T. Strickland, Dudley K. Zhang, Li |
| Copyright Year | 2006 |
| Abstract | Migration of activated macrophages is essential for resolution of acute inflammation and the initiation of adaptive immunity. Here, we show that efficient macrophage migration in inflammatory environment depends on Mac-1 recognition of a binary complex consisting of fibrin within the provisional matrix and the protease tPA (tissue-type plasminogen activator). Subsequent neutralization of tPA by its inhibitor PAI-1 enhances binding of the integrin–protease–inhibitor complex to the endocytic receptor LRP (lipoprotein receptor-related protein), triggering a switch from cell adhesion to cell detachment. Genetic inactivation of Mac-1, tPA, PAI-1 or LRP but not the protease uPA abrogates macrophage migration. The defective macrophage migration in PAI-1-deficient mice can be restored by wild-type but not by a mutant PAI-1 that does not interact with LRP. In vitro analysis shows that tPA promotes Mac-1-mediated adhesion, whereas PAI-1 and LRP facilitate its transition to cell retraction. Our results emphasize the importance of ordered transitions both temporally and spatially between individual steps of cell migration, and support a model where efficient migration of inflammatory macrophages depends on cooperation of three physiologically prominent systems (integrins, coagulation and fibrinolysis, and endocytosis). |
| Related Links | http://dx.doi.org/10.1038/sj.emboj.7601082 |
| Ending Page | 1870 |
| Page Count | 11 |
| Starting Page | 1860 |
| File Format | |
| ISSN | 02614189 |
| e-ISSN | 14602075 |
| Journal | The EMBO Journal |
| Issue Number | 9 |
| Volume Number | 25 |
| Language | English |
| Publisher Date | 2006-05-03 |
| Access Restriction | Open |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Microbiology Medicine Molecular Biology |
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