Inhibition of cell surface mediated plasminogen activation by a monoclonal antibody against α-enolase
Inhibition of cell surface mediated plasminogen activation by a monoclonal antibody against α-enolase
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DOI：
10.1002/ajh.10299
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发表时间：
2003-04-01
影响因子：
12.8
通讯作者：
Félez, J
中科院分区：
文献类型：
--
作者：
López-Alemany, R;Longstaff, C;Félez, J
纤溶酶活性在白细胞表面上的定位在纤维蛋白溶解中以及在病理和生理过程中起关键作用，在所述病理和生理过程中，细胞必须降解细胞外基质以便迁移。纤溶酶原与白细胞细胞系的结合诱导组织型（tPA）和尿激酶型（uPA）纤溶酶原激活剂激活纤溶酶原的速率增加30- 80倍。在本研究中，我们研究了α-烯醇化酶在细胞表面纤溶酶原激活中的作用。我们生产并表征了针对纯化的α-烯醇化酶的单克隆抗体（MAb）11 G1，该单克隆抗体可消除约90%的由uPA或tPA对不同谱系的白细胞样细胞系（B淋巴细胞、T淋巴细胞、粒细胞和单核细胞）的细胞依赖性纤溶酶原激活。此外，MAb 11 G1还阻断了外周血中性粒细胞和单核细胞对纤溶酶形成的增强。相反，MAb 11 G1在纤维蛋白存在下不影响纤溶酶的产生，表明该抗体在不存在细胞的情况下不与纤维蛋白溶解组分相互作用。这些数据表明，虽然白细胞细胞显示出几种结合纤溶酶原的分子，但α-烯醇化酶负责促进白细胞细胞表面上的纤溶酶原活化。(C)2003 Wiley-Liss，Inc.
Localization of plasmin activity on leukocyte surfaces plays a critical role in fibrinolysis as well as in pathological and physiological processes in which cells must degrade the extracellular matrix in order to migrate. The binding of plasminogen to leukocytic cell lines induces a 30- to 80-fold increase in the rate of plasminogen activation by tissue-type (tPA) and urokinase-type (uPA) plasminogen activators. In the present study we have examined the role of alpha-enolase in plasminogen activation on the cell surface. We produced and characterized a monoclonal antibody (MAb) 11G1 against purified alpha-enolase, which abrogated about 90% of cell-dependent plasminogen activation by either uPA or tPA on leukocytoid cell lines of different lineages: B-lymphocytic, T-lymphocytic, granulocytic, and monocytic cells. In addition, MAb11G1 also blocked enhancement of plasmin formation by peripheral blood neutrophils and monocytes. In contrast, MAb11G1 did not affect plasmin generation in the presence of fibrin, indicating that this antibody did not interact with fibrinolytic components in the absence of cells. These data suggest that, although leukocytic cells display several molecules that bind plasminogen, alpha-enolase is responsible for the majority of the promotion of plasminogen activation on the surfaces of leukocytic cells. (C) 2003 Wiley-Liss, Inc.