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Inflammation

, 32:393 | Cite as

Association of Ang-2 with Integrin β2 Controls Ang-2/PDGF-BB-Dependent Upregulation of Human Peripheral Blood Monocyte Fibrinolysis

  • Louise Bezuidenhout
  • Peter Zilla
  • Neil DaviesEmail author
Article

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.

KEY WORDS

intergrins invasion matrix metalloproteinases proteases wound healing 

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, Department of Health SciencesUniversity of Cape TownCape TownSouth Africa

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