Association of Ang-2 with integrin beta 2 controls Ang-2/PDGF-BB-dependent upregulation of human peripheral blood monocyte fibrinolysis.
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.
Bezuidenhout
Louise
L
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.
Zilla
Peter
P
Davies
Neil
N
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*
D042702:Angiopoietin-2; D018821:CD18 Antigens; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D005337:Fibrin