ANTITHROMBOTIC EFFECT OF RECOMBINANT HUMAN SOLUBLE THROMBOMODULIN ON ENDOTOXIN-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION IN RATS

被引:50
作者
GONDA, Y [1 ]
HIRATA, S [1 ]
SAITOH, K [1 ]
AOKI, Y [1 ]
MOHRI, M [1 ]
GOMI, K [1 ]
SUGIHARA, T [1 ]
KIYOTA, T [1 ]
YAMAMOTO, S [1 ]
ISHIDA, T [1 ]
MARUYAMA, I [1 ]
机构
[1] KAGOSHIMA UNIV, SCH MED, DEPT CLIN LAB MED, KAGOSHIMA 890, JAPAN
关键词
THROMBOMODULIN; DIC; HEPARIN; ENDOTOXIN;
D O I
10.1016/0049-3848(93)90201-X
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Thrombomodulin (TM) is an endothelial cell membrane glycoprotein which neutralizes thrombin procoagulant activity and accelerates the thrombin-catalyzed activation of protein C. We expressed recombinant human soluble TM (rhs-TM) in Chinese hamster ovary cells and compared the effects of rhs-TM and heparin on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats. Experimental DIC was induced by a continuous intravenous infusion of endotoxin for four hours. rhs-TM or heparin was infused simultaneously with endotoxin. Treatment with rhs-TM significantly reversed the endotoxin-induced changes in the following parameters: platelet count, fibrinogen level and fibrinogen and fibrin degradation products. Furthermore, glomerular fibrin deposits elevated by endotoxin treatment were reduced by the rhs-TM administration. Heparin showed the similar effects to rhs-TM. Activated partial thromboplastin time (APTT) in rats receiving rhs-TM were slightly longer than APTT in endotoxin-treated rats, but rats receiving heparin had much more prolonged APTT. From these results, we concluded that rhs-TM may be useful for the clinical treatment of DIC while having only minor adverse effects on APTT.
引用
收藏
页码:325 / 335
页数:11
相关论文
共 29 条
[11]  
FOUW NJ, 1988, THROMB HAEMOSTASIS, V60, P328
[12]  
FRATANTONI JC, 1975, BLOOD, V45, P395
[13]  
GOMI K, 1990, BLOOD, V75, P1396
[14]   THROMBIN-INDUCED INTRAVASCULAR COAGULATION - ROLE IN VASCULAR INJURY [J].
KAPLAN, JE ;
MALIK, AB .
SEMINARS IN THROMBOSIS AND HEMOSTASIS, 1987, 13 (04) :398-415
[15]   THROMBOMODULIN IS FOUND ON ENDOTHELIUM OF ARTERIES, VEINS, CAPILLARIES, AND LYMPHATICS, AND ON SYNCYTIOTROPHOBLAST OF HUMAN-PLACENTA [J].
MARUYAMA, I ;
BELL, CE ;
MAJERUS, PW .
JOURNAL OF CELL BIOLOGY, 1985, 101 (02) :363-371
[16]   ENDOTOXIN ENHANCES TISSUE FACTOR AND SUPPRESSES THROMBOMODULIN EXPRESSION OF HUMAN VASCULAR ENDOTHELIUM INVITRO [J].
MOORE, KL ;
ANDREOLI, SP ;
ESMON, NL ;
ESMON, CT ;
BANG, NU .
JOURNAL OF CLINICAL INVESTIGATION, 1987, 79 (01) :124-130
[17]  
NAWA K, 1992, THROMB HAEMOSTASIS, V67, P366
[18]  
OWEN WG, 1981, J BIOL CHEM, V256, P5532
[19]   MOLECULAR EVENTS INVOLVED IN THE PROAGGREGATING EFFECT OF HEPARIN ON HUMAN-PLATELETS [J].
RUGGIERO, M ;
FEDI, S ;
BIANCHINI, P ;
VANNUCCHI, S ;
CHIARUGI, V .
BIOCHIMICA ET BIOPHYSICA ACTA, 1984, 802 (02) :372-377
[20]   GENE STRUCTURE OF HUMAN THROMBOMODULIN, A COFACTOR FOR THROMBIN-CATALYZED ACTIVATION OF PROTEIN-C [J].
SHIRAI, T ;
SHIOJIRI, S ;
ITO, H ;
YAMAMOTO, S ;
KUSUMOTO, H ;
DEYASHIKI, Y ;
MARUYAMA, I ;
SUZUKI, K .
JOURNAL OF BIOCHEMISTRY, 1988, 103 (02) :281-285