单克隆抗体对尿激酶活性的抑制及对尿激酶受体结合的预防作用。

Inhibition of urokinase activity and prevention of urokinase receptor binding by monoclonal antibodies.

作者信息

Zacharias U, Handschack W, Schneider F, Löster K, Kleitke C, Noll F, Will H

机构信息

Central Institute of Molecular Biology, Academy of Sciences of the GDR, Berlin-Buch.

出版信息

J Immunol Methods. 1990 Jun 12;130(1):81-90. doi: 10.1016/0022-1759(90)90302-c.

DOI:10.1016/0022-1759(90)90302-c

PMID:2162894

Abstract

Two murine monoclonal antibodies produced against human urokinase-type plasminogen activator were characterized with respect to their antigen-binding specificity and their effects on urokinase activity and urokinase receptor binding. One of the antibodies binds to the protease domain of urokinase (Kass = 2.1 X 10(7) M-1). Antibody binding inhibits catalysis of plasminogen activation. It does not, however, affect amidolytic activity of urokinase towards the chromogenic substrate D-Val-Leu-Arg-p-nitroanilide. The antibody thus appears to interfere with plasminogen binding without directly affecting catalytically active amino acid residues of the enzyme. The other antibody binds to the aminoterminal fragment of urokinase (Kass = 1.0 X 10(7) M-1) and prevents binding of the enzyme to high affinity receptors on human granulocytes. Binding of this antibody neither influences plasminogen activation nor the amidolytic activity of urokinase. Both antibodies are potentially useful for the further analysis and manipulation of urokinase function.

摘要

针对人尿激酶型纤溶酶原激活剂产生的两种鼠单克隆抗体，就其抗原结合特异性以及对尿激酶活性和尿激酶受体结合的影响进行了表征。其中一种抗体与尿激酶的蛋白酶结构域结合（亲和常数Kass = 2.1×10⁷ M⁻¹）。抗体结合抑制纤溶酶原激活的催化作用。然而，它并不影响尿激酶对发色底物D-缬氨酸-亮氨酸-精氨酸-对硝基苯胺的酰胺水解活性。因此，该抗体似乎干扰了纤溶酶原的结合，而没有直接影响该酶的催化活性氨基酸残基。另一种抗体与尿激酶的氨基末端片段结合（亲和常数Kass = 1.0×10⁷ M⁻¹），并阻止该酶与人粒细胞上的高亲和力受体结合。这种抗体的结合既不影响纤溶酶原激活，也不影响尿激酶的酰胺水解活性。这两种抗体都可能有助于尿激酶功能的进一步分析和调控。