Enhanced binding of tissue factor-microparticles to collagen-IV and fibronectin leads to increased tissue factor activity in vitro

Ettelaie, Camille; Collier, Mary E W; Mei, Mah Pui; Xiao, Yu Pei; Maraveyas, Anthony

Abstract

The role of tissue factor (TF)-containing microparticles in clot propagation has been established, but the ability of circulating microparticles to initiate coagulation has been disputed. However, TF-bearing microparticles, particularly endothelial-microparticles generated during disease, may interact with extracellular matrices which in turn can localise circulating TF to sites of injury. In order to examine this hypothesis in vitro , microparticles were isolated from human coronary artery endothelial cells transfected to overexpress TF, tumour-necrosis factor (TNF)α-treated cells or non-transfected cells lacking TF. The ability of microparticles to bind collagen-IV, fibronectin and fibrin was examined under static conditions and arterial shear rates (650 s⁻¹ ), and also in the presence of inhibitory antibodies against β1-, β3-, α3- and αv-integrins or an anti-TF antibody. TF-microparticles showed increases of up to 43% and 24% in adherence to collagen-IV and fibronectin, respectively, compared to control microparticles under shear flow. Furthermore, TF-containing microparticles, but not the transfected parent cells had increased levels of β1-integrin compared to TF-deficient microparticles. Pre-incubation of microparticles with a β1-integrin-blocking antibody counteracted the additional adhesion of TF-microparticles compared to control microparticles. Finally, adherence of TF microparticles to collagen-IV or fibronectin resulted in increased TF activity by concentrating TF onto the surface. In conclusion, the presence of TF within microparticles enhances the interactions of endothelial cell-derived microparticles with extracellular matrices in an integrin-dependent manner. Accumulation and localisation of these microparticles in turn results in the enhancement of TF activity. This may be an innate mechanism by which TF-bearing microparticles induce coagulation upon vascular injury.

Citation

Ettelaie, C., Collier, M. E. W., Mei, M. P., Xiao, Y. P., & Maraveyas, A. (2013). Enhanced binding of tissue factor-microparticles to collagen-IV and fibronectin leads to increased tissue factor activity in vitro. Thrombosis and haemostasis, 109(1), 61-71. https://doi.org/10.1160/TH12-05-0279

• Journal Article Type: Article
• Online Publication Date: Nov 15, 2012
• Publication Date: Jan 18, 2013
• Deposit Date: Nov 13, 2014
• Journal: Thrombosis And Haemostasis
• Print ISSN: 0340-6245
• Publisher: Schattauer
• Peer Reviewed: Peer Reviewed
• Volume: 109
• Issue: 1
• Pages: 61-71
• DOI: https://doi.org/10.1160/TH12-05-0279
• Keywords: Hematology
• Public URL: https://hull-repository.worktribe.com/output/468871