Thrombomodulin Is a Cofactor for Thrombin Degradation of Recombinant Single-Chain Urokinase Plasminogen Activator "In Vitro" and in a Perfused Rabbit Heart Model

Author:

Molinari Antonio1,Giorgetti Carla1,Lansen Jacqueline1,Vaghi Fabrizio1,Orsini Gaetano2,Faioni Elena Maria3,Mannucci Pier Mannuccio3

Affiliation:

1. The Haemostasis Unit, Cardiovascular Line, IRCCS Maggiore Hospital and University of Milano, Italy

2. Biotechnology Department, R & D, Farmitalia Carlo Erba, Erbamont Group, IRCCS Maggiore Hospital and University of Milano, Italy

3. Angelo Bianchi Bonomi, Haemophilia and Thrombosis Center and Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milano, Italy

Abstract

SummaryThrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) to a two-chain derivative (tcu-PA) fibrinolyti-cally inactive. This reaction was accelerated in vitro by purified rabbit lung thrombomodulin in equimolar complex with thrombin. Polyclonal antibodies to rabbit thrombomodulin prevented this effect.We also observed that heparin and other sulfated polysaccharides had an accelerating effect on thrombin cleavage of recombinant scu-PA. Their effect was concentration-dependent and then reversed at high levels. The effect of heparin and heparan sulfate was independent and synergic with respect to thrombomodulin. All observations except the effect of heparin, could be confirmed in a Langendorff isolated rabbit heart model. From competition experiments carried out with scu-PA derivatives and mutants, we postulate that the amino-terminal sequence of rscu-PA, containing the epidermal growth factor (EGF)-like and the kringle domains is involved in the cofactor effect of thrombomodulin on scu-PA inactivation by thrombin. We conclude that a regulatory mechanism of scu-PA inactivation is present at the cell surface.

Publisher

Georg Thieme Verlag KG

Subject

Hematology

Cited by 22 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3