title: Association of Ang-2 with integrin beta 2 controls Ang-2/PDGF-BB-dependent upregulation of human peripheral blood monocyte fibrinolysis.
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.
authors.affiliation: 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.
authors.forename: Louise
authors.initials: L
authors.lastname: Bezuidenhout
authors.forename: Peter
authors.initials: P
authors.lastname: Zilla
authors.forename: Neil
authors.initials: N
authors.lastname: Davies
mesh_terms: D042702:Angiopoietin-2 / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D000077214:Becaplermin; D018821:CD18 Antigens / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D005337:Fibrin; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D051379:Mice; D009000:Monocytes / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D042702:Angiopoietin-2; D018821:CD18 Antigens; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D005337:Fibrin