Modulation of contact system proteases by glycosaminoglycans - Selective enhancement of the inhibition of factor XIa

被引:90
作者
Wuillemin, WA
Eldering, E
Citarella, F
deRuig, CP
tenCate, H
Hack, CE
机构
[1] UNIV AMSTERDAM,CENT LAB,NETHERLANDS RED CROSS BLOOD TRANSFUS SERV,AMSTERDAM,NETHERLANDS
[2] UNIV AMSTERDAM,CLIN & EXPTL IMMUNOL LAB,AMSTERDAM,NETHERLANDS
[3] UNIV ROMA LA SAPIENZA,DIPARTIMENTO BIOPATOL UMANA,SEZ BIOL CELLULARE,I-00161 ROME,ITALY
[4] UNIV AMSTERDAM,ACAD MED CTR,CTR HEMOSTASIS THROMBOSIS ATHEROSCLEROSIS & I,1066 CX AMSTERDAM,NETHERLANDS
[5] SLOTERVAART HOSP,DEPT INTERNAL MED,1066 CX AMSTERDAM,NETHERLANDS
[6] FREE UNIV AMSTERDAM HOSP,DEPT INTERNAL MED,1081 HV AMSTERDAM,NETHERLANDS
关键词
D O I
10.1074/jbc.271.22.12913
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We investigated the influence of dextran sulfate, heparin, heparan sulfate, and dermatan sulfate on the inhibition of FXIa (where FXIa is activated factor XI, for example), FXIIa, and kallikrein by C1 inhibitor, alpha(1)-antitrypsin, alpha(2)-antiplasmin, and antithrombin III. The second-order rate constants for the inhibition of FXIa by C1 inhibitor, alpha(1)-antitrypsin, alpha(2)-antiplasmin, and antithrombin III, in the absence of glycosaminoglycans, were 1.8, 0.1, 0.43, and 0.32 x 10(3) M(-1) s(-1) respectively. The rate constants of the inactivation df FXIa by C1 inhibitor and by antithrombin III increased up to 117-fold in the presence of glycosaminoglycans. These data predicted that considering the plasma concentration of the inhibitors, C1 inhibitor would be the main inhibitor of FXIa in plasma in the presence of glycosaminoglycans. Results of experiments in which the formation of complexes between serine protease inhibitors and FXIa was studied in plasma agreed with this prediction. Glycosaminoglycans did not enhance the inhibition of alpha-FXIIa, beta-FXIIa, or kallikrein by C1 inhibitor. Thus, physiological glycosaminoglycans selectively enhance inhibition of FXIa without affecting the activity of FXIIa and kallikrein, suggesting that glycosaminoglycans may modulate the biological effects of contact activation, by inhibiting intrinsic coagulation without affecting the fibrinolytic potential of FXIIa/kallikrein.
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页码:12913 / 12918
页数:6
相关论文
共 48 条
[1]  
AUSPRUNK DH, 1981, AM J PATHOL, V103, P353
[2]  
BEELER DL, 1986, BLOOD, V67, P1488
[3]   PROTEINASE - PROTEIN INHIBITOR INTERACTIONS [J].
BODE, W ;
HUBER, R .
FIBRINOLYSIS, 1994, 8 :161-171
[4]  
BOUMA BN, 1983, BLOOD, V62, P1123
[5]  
BOUMA BN, 1977, J BIOL CHEM, V252, P6432
[6]   GLYCOSAMINOGLYCANS AND THE REGULATION OF BLOOD-COAGULATION [J].
BOURIN, MC ;
LINDAHL, U .
BIOCHEMICAL JOURNAL, 1993, 289 :313-330
[7]   SURFACE-MEDIATED DEFENSE REACTIONS - THE PLASMA CONTACT ACTIVATION SYSTEM [J].
COLMAN, RW .
JOURNAL OF CLINICAL INVESTIGATION, 1984, 73 (05) :1249-1253
[8]   ANTICOAGULANT ACTION OF HEPARIN [J].
DAMUS, PS ;
HICKS, M ;
ROSENBERG, RD .
NATURE, 1973, 246 (5432) :355-357
[9]   THE COAGULATION CASCADE - INITIATION, MAINTENANCE, AND REGULATION [J].
DAVIE, EW ;
FUJIKAWA, K ;
KISIEL, W .
BIOCHEMISTRY, 1991, 30 (43) :10363-10370
[10]  
DORS DM, 1992, THROMB HAEMOSTASIS, V67, P644