Erickson L A, Hekman C M, Loskutoff D J
Proc Natl Acad Sci U S A. 1985 Dec;82(24):8710-4. doi: 10.1073/pnas.82.24.8710.
Monospecific antiserum to an unusually stable Mr 50,000 plasminogen-activator inhibitor (PAI) purified from cultured bovine aortic endothelial cells was employed in conjunction with reverse fibrin autography to determine whether human platelets, serum, and plasma contain immunologically related inhibitors. Reverse fibrin autography revealed the presence of a Mr 50,000 inhibitor in the platelet and serum samples but not in normal plasma. However, a Mr 50,000 inhibitor was detected in plasma obtained from individuals with increased PAI activity. In each case, treatment of the sample with the anti-inhibitor serum removed the Mr 50,000 inhibitor. The inhibitor present in each sample neutralized exogenously added tissue-type plasminogen activator in a rapid manner. Inhibition was associated with the formation of a NaDodSO4-resistant enzyme-inhibitor complex of Mr 120,000. Again, treatment of the samples with the anti-inhibitor serum removed both the inhibitory activity and the component in these samples that binds to tissue-type plasminogen activator. Thus, the rapidly acting PAI present in human platelets, serum, and patient plasma is immunologically related to the PAI synthesized by cultured bovine aortic endothelial cells. This molecule may be the physiologically relevant inhibitor of plasminogen activator in the vascular system and, as such, may serve an important role in regulating the initiation of vascular fibrinolysis.
从培养的牛主动脉内皮细胞中纯化出一种异常稳定的50,000道尔顿的纤溶酶原激活物抑制剂(PAI),使用针对该抑制剂的单特异性抗血清,结合反向纤维蛋白自显影技术,来确定人血小板、血清和血浆中是否含有免疫相关的抑制剂。反向纤维蛋白自显影显示,血小板和血清样品中存在一种50,000道尔顿的抑制剂,但正常血浆中没有。然而,在PAI活性增加的个体的血浆中检测到了一种50,000道尔顿的抑制剂。在每种情况下,用抗抑制剂血清处理样品都会去除50,000道尔顿的抑制剂。每个样品中存在的抑制剂能迅速中和外源性添加的组织型纤溶酶原激活物。抑制作用与形成一种120,000道尔顿的耐十二烷基硫酸钠的酶-抑制剂复合物有关。同样,用抗抑制剂血清处理样品会去除这些样品中的抑制活性以及与组织型纤溶酶原激活物结合的成分。因此,人血小板、血清和患者血浆中存在的快速作用的PAI与培养的牛主动脉内皮细胞合成的PAI在免疫上相关。这种分子可能是血管系统中纤溶酶原激活物的生理相关抑制剂,因此可能在调节血管纤维蛋白溶解的起始过程中起重要作用。