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- Title
Association of Ang-2 with Integrin β2 Controls Ang-2/PDGF-BB-Dependent Upregulation of Human Peripheral Blood Monocyte Fibrinolysis.
- Authors
Bezuidenhout, Louise; Zilla, Peter; Davies, Neil
- 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 β2, and functional inhibition of integrin β2 eliminated Ang-2/PDGF-BB-mediated upregulation of monocyte fibrin invasion. Additionally, integrin β2 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 β2. In addition, Ang-2 was shown to upregulate PDGFR-β 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.
- Subjects
VASCULAR endothelial growth factors; ANTIFIBRINOLYTIC agents; GROWTH factors; METALLOPROTEINASES; SERINE proteinases; MONOCYTES; PROTEIN-tyrosine kinases; INTEGRINS
- Publication
Inflammation, 2009, Vol 32, Issue 6, p393
- ISSN
0360-3997
- Publication type
Article
- DOI
10.1007/s10753-009-9148-9