Gaffney P J
National Institute for Biological Standards and Control, South Mimms, Herts. U.K.
Haemostasis. 1988;18 Suppl 1:47-60. doi: 10.1159/000215837.
Like a number of the components of the fibrinolytic and coagulation systems, plasminogen (plgn) is a multifunctional molecule. As a proenzyme, a number of its activities such as its binding to fibrin, histidine-rich glycoprotein (HRGP) and alpha 2-antiplasmin (AP) are expressed while its major enzymatic activity remains unexpressed. This latter activity has been used as a yardstick of plasminogen potency, despite the fact that no such activity resides in the native plasminogen molecule. Assay procedures usually involve the activation of the plasminogen to plasmin using an activator such as streptokinase (SK) or urokinase (UK) and a major problem involves the establishment of a properly-timed plasminogen-activator ratio to fully express the plasminogen as the active enzyme plasmin (Gaffney, P.J. et al. Activation of plasminogen as a feature of its assay. Haemostasis 1977, 6, 72-78). Substrates such as casein, fibrinogen and fibrin have been used to assess the plasmin activity developed while more recently the tripeptide chromogenic substrate S-2251 has been successfully used. These assays have been standardised using a reference preparation of the active enzyme, plasmin, and both a 1st and 2nd International Reference Preparation (IRP) have been established. These IRP's differed in that the fibrin binding kringle-structures were missing in the 1st IRP yielding differing fibrinolytic and chromogenic activities (Philo, R.D. and Gaffney, P.J. Plasmin potency estimates. Influence of substrate used in assay. Thrombosis and Haemostasis 1981, 45, 107-109). Activation procedures of plasminogen and subsequent assays of plasmin using a variety of substrates have been recently superseded by an assay which involves the formation of a plgn-SK complex which complex has an active site which hydrolyses the chromogenic substrate S-2251. This avoids the problems highlighted above involved in measuring plasminogen activity at the optimum stage during activation. While plasmin standards have been suitable for the standardisation of plasminogen when it is measured by activation-based procedures, a British Standard for glutamic acid-plasminogen has now been established in order to standardise the plgn-SK assay (Gaffney, P.J. and Curtis, A.D. The establishment of a standard for plasminogen (glu-type). Thrombosis and Haemostasis 1984, 51, 376-378). The calibration of this standard using the 2nd IRP for plasmin and the value of this standard in the measurement of plasminogen in plasma is discussed.
与纤维蛋白溶解和凝血系统的许多成分一样，纤溶酶原（plgn）是一种多功能分子。作为一种酶原，它的一些活性，如与纤维蛋白、富含组氨酸的糖蛋白（HRGP）和α2-抗纤溶酶（AP）的结合，在其主要酶活性未表达时就已表现出来。尽管天然纤溶酶原分子中不存在这种活性，但后一种活性已被用作纤溶酶原效力的衡量标准。检测程序通常涉及使用链激酶（SK）或尿激酶（UK）等激活剂将纤溶酶原激活为纤溶酶，一个主要问题是要建立适当的纤溶酶原-激活剂比例，以使纤溶酶原充分转化为活性酶纤溶酶（加夫尼，P.J.等人。纤溶酶原的激活作为其检测的一个特征。止血1977年，6，72 - 78）。酪蛋白、纤维蛋白原和纤维蛋白等底物已被用于评估所产生的纤溶酶活性，最近三肽发色底物S - 2251已成功使用。这些检测方法已使用活性酶纤溶酶的参考制剂进行了标准化，并且已经建立了第一和第二国际参考制剂（IRP）。这些IRP的不同之处在于，第一种IRP中缺少纤维蛋白结合kringle结构，导致纤溶和发色活性不同（菲洛，R.D.和加夫尼，P.J.纤溶酶效力估计。检测中使用的底物的影响。血栓形成与止血1981年，45，107 - 109）。纤溶酶原的激活程序以及随后使用各种底物对纤溶酶的检测最近已被一种检测方法所取代，该方法涉及形成plgn - SK复合物，该复合物具有一个活性位点，可水解发色底物S - 2251。这避免了上述在激活过程的最佳阶段测量纤溶酶原活性时所突出的问题。虽然纤溶酶标准适用于通过基于激活的程序测量纤溶酶原时的标准化，但现在已经建立了谷氨酸纤溶酶原的英国标准，以便对plgn - SK检测进行标准化（加夫尼，P.J.和柯蒂斯，A.D.纤溶酶原（谷氨酸型）标准的建立。血栓形成与止血1984年，51，376 - 378）。讨论了使用第二种纤溶酶IRP对该标准进行校准以及该标准在血浆纤溶酶原测量中的价值。
