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Stimulation of Peripheral Blood Monocyte Fibrinolysis by Ang‐2 and PDGF‐BB
Author(s) -
Bezuidenhout Louise,
Bracher Mona,
Zilla Peter,
Davies Neil
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a711
Subject(s) - fibrinolysis , monocyte , endocrinology , platelet derived growth factor receptor , angiogenesis , medicine , chemistry , growth factor , platelet derived growth factor , fibrin , inflammation , immunology , receptor
Background Angiopoietins are a family of growth factors known to play an important role in blood vessel stability. Angiopoietin‐2 (Ang‐2) is known to initiate vessel destabilization at sites of vascular remodeling. This accompanies increased vascular hyperpermeability, leading to plasma exudation and deposition of plasma proteins, such as fibrinogen, in the extracellular space. There is substantial evidence suggesting that inflammation and angiogenesis are interdependent processes, and that an inflammatory infiltrate, composed mainly of monocytes, often precedes angiogenesis. We demonstrate that Ang‐2, in conjunction with platelet‐derived growth factor (PDGF‐BB), upregulates monocyte fibrinolysis Methods Human monocytes were isolated from peripheral blood. Their fibrinolytic activity in response to Ang‐2 under serum‐containing conditions and to Ang‐2 and PDGF‐BB under serum‐free conditions was assessed by quantification of their migration through fibrin. The underlying mechanisms were investigated using protease inhibitors. Results Ang‐2 causes an upregulation of fibrinolysis in human peripheral monocytes in the presence of serum (cell migration increase relative to control: 69% p<0.05). Ang‐2 induced activity was dependent upon the presence of PDGF‐BB in the absence of serum (cell migration inc. rel. control: Ang‐2 35% p=NS; PDGF‐BB 0%; Ang‐2/PDGF‐BB 145% p<0.05). In addition, we showed that this upregulation of fibrinolysis involves both serine proteases and matrix metalloproteinases. Conclusion This suggests that early‐release cytokines, Ang‐2 and PDGF‐BB are involved in assisting the invasion of monocytes into the fibrin clot during the initial stages of tissue remodeling. (MRC SA)