Hepatocyte tissue factor activates the coagulation cascade in mice.
Blood
; 121(10): 1868-74, 2013 Mar 07.
Article
en En
| MEDLINE
| ID: mdl-23305736
ABSTRACT
In this study, we characterized tissue factor (TF) expression in mouse hepatocytes (HPCs) and evaluated its role in mouse models of HPC transplantation and acetaminophen (APAP) overdose. TF expression was significantly reduced in isolated HPCs and liver homogenates from TF(flox/flox)/albumin-Cre mice (HPC(ΔTF) mice) compared with TF(flox/flox) mice (control mice). Isolated mouse HPCs expressed low levels of TF that clotted factor VII-deficient human plasma. In addition, HPC TF initiated factor Xa generation without exogenous factor VIIa, and TF activity was increased dramatically after cell lysis. Treatment of HPCs with an inhibitory TF antibody or a cell-impermeable lysine-conjugating reagent prior to lysis substantially reduced TF activity, suggesting that TF was mainly present on the cell surface. Thrombin generation was dramatically reduced in APAP-treated HPC(ΔTF) mice compared with APAP-treated control mice. In addition, thrombin generation was dependent on donor HPC TF expression in a model of HPC transplantation. These results suggest that mouse HPCs constitutively express cell surface TF that mediates activation of coagulation during hepatocellular injury.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Coagulación Sanguínea
/
Tromboplastina
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Trombina
/
Factor VIIa
/
Hepatocitos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
/
Male
Idioma:
En
Revista:
Blood
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos