Concomitant secretion of prourokinase and of a plasminogen activator- specific inhibitor by cultured human monocytes-macrophages
Concomitant secretion of prourokinase and of a plasminogen activator- specific inhibitor by cultured human monocytes-macrophages
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培养的人单核细胞-巨噬细胞同时分泌尿激酶原和纤溶酶原激活剂特异性抑制剂
DOI：
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发表时间：
1984
影响因子：
15.3
通讯作者：
D. Belin
中科院分区：
文献类型：
--
作者：
J. Vassalli;J. Dayer;A. Wohlwend;D. Belin
新鲜纯化的人单核细胞-巨噬细胞和组织细胞、淋巴瘤来源的 U 937 细胞产生的纤溶酶原激活剂 (PA) 在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳 (SDS-PAGE) 后通过酶谱分析，发现其迁移的表观 Mr 为 55,000，与尿激酶 (Uk) 相同。通过使用针对两种不同类型 PA 的特异性抗体进行免疫沉淀，显示该酶与尿激酶具有免疫学相关性，而不是与组织 PA 相关。尿激酶以无活性的 Mr 55,000 酶原尿激酶原的形式分泌，并且可以通过纤溶酶的有限蛋白水解转化为活性的 Mr 55,000 酶。来自 U 937 细胞和单核巨噬细胞培养物的条件培养基抑制外源添加的尿激酶的纤溶活性。使用[125I]-标记的尿激酶，我们观察到酶-配体复合物的形成，该复合物不会通过在SDS中煮沸而解离，并且以比游离酶高40,000道尔顿的明显Mr迁移；由于复合尿激酶作为 PA 在功能上失活，因此配体是尿激酶的抑制剂。这种抑制剂与成纤维细胞产生的蛋白酶连接蛋白不同，它不与凝血酶相互作用。这些结果表明，单核吞噬细胞对纤溶酶原的激活可以通过酶（原）和特定抑制剂的分泌来调节。
The plasminogen activator (PA) produced by freshly purified human monocytes-macrophages and histiocytic, lymphoma-derived U 937 cells was analyzed by zymography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and found to migrate with an apparent Mr of 55,000, identical to that of urokinase (Uk). By immunoprecipitation with antibodies specific for the two different types of PA, the enzyme was shown to be immunologically related to urokinase, and not to tissue PA. Urokinase was secreted in the form of the inactive Mr 55,000 zymogen prourokinase , and could be converted to the active Mr 55,000 enzyme by limited proteolysis with plasmin. Conditioned media from cultures of U 937 cells and monocytes-macrophages inhibited the fibrinolytic activity of exogenously added urokinase. Using [125I]- labeled urokinase we observed the formation of an enzyme-ligand complex, which was not dissociated by boiling in SDS and migrated with an apparent Mr 40,000 daltons higher than the free enzyme; since complexed urokinase was functionally inactivated as a PA, the ligand is an inhibitor of urokinase. This inhibitor is different from fibroblast- produced protease- nexin , in that it did not interact with thrombin. These results suggest that plasminogen activation by mononuclear phagocytes can be modulated through the secretion of both (pro)enzyme and a specific inhibitor.
DOI：
10.1073/pnas.80.10.2956
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LOSKUTOFF, DJ;VANMOURIK, JA;LAWRENCE, D
通讯作者：
LAWRENCE, D
在角质形成细胞培养物中产生三种纤溶酶原激活剂和一种抑制剂。
DOI：
10.1016/0304-4165(83)90339-2
发表时间：
1983
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Birkedal-Hansen,H;Taylor,RE
通讯作者：
Taylor,RE
地塞米松诱导的肝癌细胞纤溶活性抑制剂。
DOI：
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发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Coleman,PL;Barouski,PA;Gelehrter,TD
通讯作者：
Gelehrter,TD