Abstract：
BACKGROUND:Activated factor X (FXa) is involved in hemostasis, thrombogenesis, inflammation, and cellular immune response. Tissue factor (TF) is an initiator of blood coagulation. We investigated whether FXa induces TF expression in human peripheral monocytes and whether treatment with FXa inhibitor reduces TF expression in an experimental model of rat endotoxemia. METHODS:Human peripheral mononuclear cells were used to determine TF expression induced by FXa. Experimental rat endotoxemia was induced by intravenous bolus injection of lipopolysaccharide (LPS). A specific FXa inhibitor, DX-9065a, was administered subcutaneously immediately after LPS injection. RESULTS:FXa induced TF expression in monocytes without intervention of thrombin and the expression was suppressed by FXa inhibitor. In the experimental model of rat endotoxemia, TF and TF mRNA expression levels in the liver were reduced by DX-9065a. Moreover, administration of DX-9065a suppressed the rise in plasma concentrations of thrombin-antithrombin III complex (TAT) and monocyte chemoattractant protein-1 (MCP-1). CONCLUSIONS:Our results indicated that FXa can induce TF expression in human peripheral monocytes and that inhibition of FXa reduces TF expression in the liver of rat endotoxemia. These results suggest that FXa is an important factor for TF expression in sepsis.
journal_name
Surgeryjournal_title
Surgeryauthors
Akahane K,Okamoto K,Kikuchi M,Todoroki H,Higure A,Ohuchida T,Kitahara K,Takeda S,Itoh H,Ohsato Kdoi
10.1067/msy.2001.116452subject
Has Abstractpub_date
2001-11-01 00:00:00pages
809-18issue
5eissn
0039-6060issn
1532-7361pii
S0039-6060(01)41891-5journal_volume
130pub_type
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