Inhibition of plasminogen activation by monoclonal antibodies to the kringle 5-B chain segment of human plasminogen.

Inhibition of plasminogen activation by monoclonal antibodies to the kringle 5-B chain segment of human plasminogen.
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通过针对人纤溶酶原的 kringle 5-B 链段的单克隆抗体抑制纤溶酶原激活。

DOI:
10.1089/hyb.1991.10.659
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发表时间:
1991
期刊:
影响因子:
--
通讯作者:
Messier,TL
Messier,TL
中科院分区:
--
文献类型:
--
作者:
Church,WR;Messier,TL

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制备了三种抗人纤溶酶原的鼠单克隆抗体(命名为α Pg-28、α Pg-96和α Pg-247)。所有三种抗体都结合纤溶酶原和由残基Val442-Asn790组成的纤溶酶原的弹性蛋白酶消化产物(微型纤溶酶原)。每种抗体识别的表位是不同的。在纤维蛋白平板试验中,抗体α Pg-96和α Pg-247阻断组织纤溶酶原激活物依赖性溶解,而抗体α Pg-28无作用。抗体α Pg-96阻断尿激酶和组织纤溶酶原激活剂催化的和链激酶介导的纤溶酶原激活。抗体α Pg-28和α Pg-247部分抑制组织纤溶酶原激活物催化的纤溶酶原激活。抗体α Pg-28和α Pg-247也抑制链激酶介导的纤溶酶原激活,但不抑制尿激酶催化的激活。抗体α Pg-247通过降低合成底物S-2251的Vmax并使纤溶酶的Km增加4倍来抑制纤溶酶对底物S-2251的催化。其他抗体对纤溶酶活性无显著影响。纤溶酶原激活的这种差异性抑制表明,尿激酶、组织纤溶酶原激活剂和链激酶的激活可能涉及微纤溶酶原结构的不同区域。
Three murine monoclonal antibodies (designated αPg-28, αPg-96, and αPg-247) against human plasminogen were prepared. All three antibodies bound plasminogen and the elastase-digestion product of plasminogen consisting of residues Val442-Asn790(miniplasminogen). The epitopes recognized by each antibody were distinct. Antibodies αPg-96 and αPg-247 blocked tissue plasminogen activator-dependent lysis in a fibrin plate assay while antibody αPg-28 had no effect. Antibody αPg-96 blocked urokinase- and tissue plasminogen activator-catalyzed, and streptokinase-mediated, plasminogen activation. Antibodies αPg-28 and αPg-247 partially inhibited tissue plasminogen activator-catalyzed plasminogen activation. Antibodies αPg-28 and αPg-247 also inhibited streptokinase-mediated plasminogen activation, but not urokinasecatalyzed activation. Antibody αPg-247 inhibited plasmin catalysis of substrate S-2251 by decreasing the VMAXand increasing the KMof plasmin for the synthetic substrate S-2251 four-fold. The other antibodies had no significant effect on plasmin activity. This differential inhibition of plasminogen activation suggests that activation by urokinase, tissue plasminogen activator, and streptokinase possibly involve distinct regions of miniplasminogen structure.
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