A key role for Toll-like receptor-3 in disrupting the hemostasis balance on endothelial cells

Aya S.,et al. Blood 113, 714-722, 2009

Speaker: Hsieh-Chi Lu(呂學奇)                                    Time: 15:10~16:00, Jun. 10, 2009

Commentator: Dr. Chiou-Feng Lin (林秋烽博士)       Place: Room 601

Abstract:

Most viral infections can cause the imbalance of hemostasis and some of them induce the viral hemorrhagic fever (VHF). The VHF-causing viruses are normally replicated in endothelial cells (EC)(1)，dendritic cells，and monocytes. A previous study showed the infection of Ebola virus increases tissue factor (TF)expression(towards coagulation pathway)(2). In this paper，the authors used polyI:C to mimic the viral infection. They found that polyI:C promoted TF expression and decreased thrombomodulin(TM) expression on endothelial cells，but not on monocytes. However，cytokines were produced both from endothelial cells and from monocytes by polyI:C. The clotting time was also reduced on endothelial cells treated by polyI:C. Some of pathogen sensors can sense the virus in innate immunity. The authors proved that TLR3 mediated the polyI:C-induced change of cellular hemostasis in vivo and in vitro. In vivo test，D-Dimer，a fibrin degradation product，decreased in TLR3^-/- mice but some cytokine productions(TNF-α，IL-6)seemed no variation in WT mice and in TLR3^-/- mice. The histological results also demonstrated the fibrin deposite，TF production and TM reduction in WT mice but not in TLR3^-/- mice. Therefore，detection of polyI:C via TLR3 can influence the coagulation and fibrinolysis on endothelial cells.

References:

1.Peters CJ, Zaki SR. Role of the endothelium in viral hemorrhagic fevers. Crit Care Med.;30:S268-S273,(2002).

2.Geisbert TW, Young HA, Jahrling PB, Davis KJ,Kagan E, Hensley LE. Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event. J Infect Dis.;188:1618-1629, (2003).