Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor-dependent procoagulant activity

Blood. 2002 Jun 1;99(11):3962-70. doi: 10.1182/blood.v99.11.3962.

Abstract

In the present study we investigated whether endothelial microparticles (EMPs) can bind to monocytic THP-1 cells and modulate their procoagulant properties. Using flow cytometry, we demonstrated that EMPs express adhesive receptors similar to those expressed by activated endothelial cells. Expression of endothelial antigens by THP-1 cells incubated with EMP was shown by immunoperoxidase staining and flow cytometry using antibodies directed against E-selectin, VCAM-1, and endoglin. EMP binding to THP-1 cells was time- and concentration- dependent, reached a plateau at 15 minutes, and had an EMP-to-monocyte ratio of 50:1. EMP binding was not affected by low temperature and was not followed by the restoration of phosphatidylserine asymmetry, suggesting that adhesion was not followed by fusion. A 4-hour incubation of THP-1 cells with EMP led to an increase in procoagulant activity as measured by clotting assay. Concomitantly, THP-1 exhibited increased levels of tissue factor (TF) antigen and TF mRNA compared to control cells. The ability of EMP to induce THP-1 procoagulant activity was significantly reduced when THP-1 cells were incubated with EMP in the presence of blocking antibodies against ICAM-1 and beta2 integrins. These results demonstrate that EMPs interact with THP-1 cells in vitro and stimulate TF-mediated procoagulant activity that is partially dependent on the interaction of ICAM-1 on EMP and its counterreceptor, beta2 integrins, on THP-1 cells. Induction of procoagulant activity was also demonstrated using human monocytes, suggesting a novel mechanism by which EMP may participate in the dissemination and amplification of procoagulant cellular responses.

MeSH terms

  • Blood Coagulation Factors / analysis
  • Blood Coagulation Factors / biosynthesis*
  • Cell Adhesion
  • Cell Line
  • Cells, Cultured
  • Endothelium, Vascular / physiology*
  • Humans
  • Monocytes / physiology*
  • Recombinant Proteins / pharmacology
  • Thromboplastin / pharmacology*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Umbilical Veins

Substances

  • Blood Coagulation Factors
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • leukocyte procoagulant activity
  • Thromboplastin