Sane D C, Moser T L, Greenberg C S
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Thromb Haemost. 1991 Sep 2;66(3):310-4.
Vitronectin (VN) stabilizes plasminogen activator inhibitor type 1 (PAI-1) activity and prevents the fibrin(ogen)-induced acceleration of plasminogen activation by t-PA. These antifibrinolytic activities as well as other functions are mediated by the glycosaminoglycan (GAG) binding domain of VN. Since the GAG binding region is rich in arginyl and lysyl residues, it is a potential target for enzymes such as plasmin. In this paper, the dose and time-dependent proteolysis of VN by plasmin is demonstrated. The addition of urokinase or streptokinase (200 units/ml) to plasma also produced proteolysis of VN. With minimal proteolysis, the 75 kDa band was degraded to a 62-65 kDa form of VN. This minimal proteolysis destroyed the binding of [3H]-heparin to VN and reversed the neutralization of heparin by VN. Thus, the plasmin-mediated proteolysis of the GAG binding activity of VN could destroy the antifibrinolytic activity of VN during physiologic conditions and during thrombolytic therapy. Furthermore, other functions of VN in complement and coagulation systems that are mediated by the GAG binding domain may be destroyed by plasmin proteolysis.
玻连蛋白（VN）可稳定1型纤溶酶原激活物抑制剂（PAI-1）的活性，并阻止纤维蛋白（原）诱导的组织型纤溶酶原激活物（t-PA）加速纤溶酶原激活。这些抗纤溶活性以及其他功能是由VN的糖胺聚糖（GAG）结合域介导的。由于GAG结合区域富含精氨酰和赖氨酰残基，它是诸如纤溶酶等酶的潜在作用靶点。本文证实了纤溶酶对VN的剂量和时间依赖性蛋白水解作用。向血浆中添加尿激酶或链激酶（200单位/毫升）也会导致VN的蛋白水解。在最小程度的蛋白水解作用下，75 kDa条带降解为62 - 65 kDa形式的VN。这种最小程度的蛋白水解破坏了[3H] - 肝素与VN的结合，并逆转了VN对肝素的中和作用。因此，纤溶酶介导的VN的GAG结合活性的蛋白水解作用可能在生理条件下和溶栓治疗期间破坏VN的抗纤溶活性。此外，VN在补体和凝血系统中的其他由GAG结合域介导的功能可能会被纤溶酶的蛋白水解作用破坏。
