Recombinant Human Thrombomodulin Attenuates Human Endothelial Cell Activation by Human Thrombin
作者:
John Parkinson,
Nils Bang,
Joe Garcia,
期刊:
Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
(OVID Available online 1993)
卷期:
Volume 13,
issue 7
页码: 1119-1123
ISSN:1049-8834
年代: 1993
出版商: OVID
关键词: inositol phosphates;permeability;prostacyclin
数据来源: OVID
摘要:
Two glycoforms of recombinant human thrombomodulin (TM; TMD1-105 and TMD1-75), an endothelial cell membrane protein, were tested for their ability to alter thrombin-induced activation of cultured human umbilical vein endothelial cells (HUVECs). After stimulation with 10 nmol/L thrombin, HUVEC generation of inositol-l,4,5-trisphosphate (IP}), a potent Ca$-mobilizing second messenger, was dosedependently blocked by TMD1-105. Both TMD1-105 (ICM= 10 nmol/L) and TMD1-75 (ICjo=100 nmol/L) blocked the enhanced prostacyclin synthesis by HUVEC monolayers treated with 10 nmol/L thrombin. HUVEC monolayer permeability to Evans blue dye-labeled albumin increased from 0.125 ±0.06 /iL/min in control experiments to 0J80±0.09 jtL/min after treatment with 100 nmol/L thrombin (p<.05). Incubation or HUVECs with TMD1-105 alone (600 nmol/L) had no effect (0.114±0.04fiL/min)on basal permeability. In contrast, incubation of 100 nmol/L thrombin with 600 nmol/L TMD1-105 reduced this increase in HUVEC permeability to almost control levels (0.142±0.06 /tL/min). These results demonstrate that recombinant human TM, a potent in vitro anticoagulant, also functions as an antagonist of thrombin receptor-mediated HUVEC activation. In addition to its anticoagulant functions, the highaffinity endothelial cell receptor TM may play a role in modulating endothelial cell activation by thrombin.
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