PMID- 11685190
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20141120
IS  - 0039-6060 (Print)
IS  - 0039-6060 (Linking)
VI  - 130
IP  - 5
DP  - 2001 Nov
TI  - Inhibition of factor Xa suppresses the expression of tissue factor in human 
      monocytes and lipopolysaccharide-induced endotoxemia in rats.
PG  - 809-18
AB  - 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.
FAU - Akahane, K
AU  - Akahane K
AD  - Department of Surgery I, University of Occupational and Environmental Health, 1-1 
      Iseigaoka, Yahatanishi-ku, Kitakyushu, Japan.
FAU - Okamoto, K
AU  - Okamoto K
FAU - Kikuchi, M
AU  - Kikuchi M
FAU - Todoroki, H
AU  - Todoroki H
FAU - Higure, A
AU  - Higure A
FAU - Ohuchida, T
AU  - Ohuchida T
FAU - Kitahara, K
AU  - Kitahara K
FAU - Takeda, S
AU  - Takeda S
FAU - Itoh, H
AU  - Itoh H
FAU - Ohsato, K
AU  - Ohsato K
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Surgery
JT  - Surgery
JID - 0417347
RN  - 0 
      ((2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic 
      acid)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Naphthalenes)
RN  - 0 (Propionates)
RN  - 0 (RNA, Messenger)
RN  - 9035-58-9 (Thromboplastin)
RN  - EC 3.4.21.6 (Factor Xa)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/blood
MH  - Endotoxemia/*metabolism
MH  - Factor Xa/physiology
MH  - *Factor Xa Inhibitors
MH  - Humans
MH  - Immunohistochemistry
MH  - Lipopolysaccharides/*toxicity
MH  - Liver/metabolism
MH  - Male
MH  - Monocytes/*metabolism
MH  - Naphthalenes/*pharmacology
MH  - Propionates/*pharmacology
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Thromboplastin/*biosynthesis/genetics
EDAT- 2001/10/31 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/31 10:00
PHST- 2001/10/31 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/31 10:00 [entrez]
AID - S0039-6060(01)41891-5 [pii]
AID - 10.1067/msy.2001.116452 [doi]
PST - ppublish
SO  - Surgery. 2001 Nov;130(5):809-18. doi: 10.1067/msy.2001.116452.