| Title | Association of Ang-2 with Integrin beta2 Controls Ang-2/PDGF-BB-Dependent Upregulation of Human Peripheral Blood Monocyte Fibrinolysis. | | Author(s) | Bezuidenhout L, Zilla P, Davies N | | Institution | Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, Department of Health Sciences, University of Cape Town, 203 Cape Heart Centre, Anzio Road, Observatory, 7925, Cape Town, South Africa. | | Source | Inflammation 2009 Sep 2. | | Abstract | Angiopoietin-2 (Ang-2), an angiogenic factor that is generally considered an autocrine factor for endothelial cells was shown in a previous study to upregulate peripheral blood monocyte fibrinolysis in concert with platelet-derived growth factor-BB (PDGF-BB). This upregulation of fibrinolysis was demonstrated to be due to upregulation of elements of the matrix metalloproteinase and serine protease fibrinolytic pathways. The manner in which Ang-2 interacts with monocytes was not elucidated though no expression of the angiopoietin receptor tyrosine kinase Tie-2 was found for monocytes. In this study Ang-2 was found to bind to integrin beta(2), and functional inhibition of integrin beta(2) eliminated Ang-2/PDGF-BB-mediated upregulation of monocyte fibrin invasion. Additionally, integrin beta(2) blockade significantly inhibited the Ang-2/PDGF-BB based increase in matrix metalloproteinase-9 (MMP-9) and membrane type-1-MMP (MT1-MMP). Furthermore, Ang-2/PDGF-BB-upregulated urokinase plasminogen-activator receptor (uPAR) was shown to be associated in complexes with integrin beta(2). In addition, Ang-2 was shown to upregulate PDGFR-beta expression in monocytes. Therefore several components of the mechanism via which the novel interaction of Ang-2 and PDGF-BB with monocytes occurs have been identified. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19728062 |
|
