Inhibition of lipopolysaccharide-induced tissue factor expression in monocytes by urinary trypsin inhibitor in vitro and in vivo

Perenlei Molor-Erdene; Kenji Okajima; Hirotaka Isobe; Mitsuhiro Uchiba; Naoaki Harada; Nobuhiko Shimozawa; Hiroaki Okabe

doi:10.1160/TH04-09-0577

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2005; 94(01): 136-145
DOI: 10.1160/TH04-09-0577

Platelets and Blood Cells

Schattauer GmbH

Inhibition of lipopolysaccharide-induced tissue factor expression in monocytes by urinary trypsin inhibitor in vitro and in vivo

Perenlei Molor-Erdene

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Kenji Okajima

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Hirotaka Isobe

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Mitsuhiro Uchiba

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Naoaki Harada

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Nobuhiko Shimozawa

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

,

Hiroaki Okabe

¹Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

› Institutsangaben

Abstract

Summary

Tissue factor (TF) plays a critical role in the pathogenesis of disseminated intravascular coagulation (DIC) observed in patients with septic shock. Urinary trypsin inhibitor (UTI), a multivalent protease inhibitor, is currently used for treatment of patients with septic shock. This study was undertaken to determine whether UTI reduces LPS-induced coagulation abnormalities by inhibiting lipopolysaccharide (LPS)-induced expression of TF by monocytes. UTI inhibited LPS-induced increases in both TF activities andTF mRNA expression in monocytes without affecting the viability. Although activation of nuclear factor-κB (NF-κB), activator protein-1 (AP-1) and extracellular signal-regulated kinase (ERK)1/2 were shown to be critically involved in LPS-induced increases in TF activities in isolated monocytes, UTI inhibited phosphorylation of ERK1/2 and decreased expression of early growth response factor-1 (Egr-1) induced by LPS without affecting the activation of NF-κB and AP-1. UTI inhibited both the expression of TF mRNA in whole blood, increases in TF activities in mononuclear cells, and increases in serum levels of fibrin and fibrinogen degradation products (E) in rats given LPS without affecting the number of monocytes in the peripheral blood. Taken together these results strongly suggested that UTI might reduce LPS-induced coagulation abnormalities in rats by inhibiting TF expression in monocytes through inhibition of Egr-1 expression.

Keywords

Tissue factor - monocytes - Egr-1 - disseminated intravascular coagulation

Volltext

Referenzen

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