HYDROLYTIC ENZYMES OF BLOOD IN HEALTH AND DISEASE

止血、激肽释放和血管紧张素的相互作用 血浆和血清补体系统中的纤溶酶 接受检查，以深入了解其中一些 酶是由血清中的C1-抑制物调节的，它调节 几种这样的酶，但对调节C1至关重要， 激活补体的第一个成分。此外，止血药 涉及高分子激肽原的事件可能会影响 血管功能，以及该激肽原与 将检查血管内皮细胞。要做到这一点，有几种方法将 使用： 1.对纯化的正常C_1-抑制物进行检测，以确定 分子的不同结构域可能参与特定的位点 与已知调节的血浆蛋白水解酶的相互作用 这种抑制剂。这种可能性很可能是因为我们之前的 研究表明异常的C1-抑制剂的异质性行为 遗传性血管神经性水肿患者的蛋白质 与正常的C1-抑制剂调节的每一种酶有关。 要做到这一点，正常的C1-抑制剂的片段 溴化氰，或通过有限的蛋白质分解消化，将是 检查它们的抑制活性和形成能力 与这些酶(X11a因子、激肽释放酶、纤溶酶、 C1S。 2.改变表达方式有多种可能的解释 遗传性血管神经性水肿中的C_1抑制基因。一 本实验室将使用的方法来深入了解这一点 问题将是比较外周血单核细胞的mRNAs 从正常人到不同类型的人 遗传性血管神经性水肿。无论是数量上还是质量上 这些患者的mrna将与正常人的mrna进行比较。 个人。 3.将检测培养的人脐静脉内皮细胞 位于人HIGH重链或轻链上的抗原 分子量激肽原。因为轻链参与了 与某些物质结合并产生促凝剂 活性，它可能在内皮膜上被鉴定，并且 可能会在可定义的状态下转移到这些细胞，在这些状态下 功能会被挑起。其他研究将审查 轻链抗原与重链抗原的血浆浓度比值 正常人和病变者血浆中hmwk的含量 涉及血管系统的状态。

lnterrelated functions of hemostatic, kinin-releasing, and fibrinolytic enzymes in plasma and the serum complement system will be examined to gain insight into the ways in which some of those enzymes are regulated by the serum C1-inhibitor, which regulates several such enzymes but is critical to the regulation of C1, the activated first component of complement. In addition, hemostatic events involving high molecular weight kininogen may affect vascular function, and the interactions between this kininogen and endothelium will be examined. To do this, several approaches will be used: 1. Purified normal C1-inhibitor will be examined to determine if different domains of the molecule may participate in site-specific interactions with the plasma proteases known to be regulated by this inhibitor. This possibility is likely because our earlier studies showed heterogeneous behavior of abnormal C1-inhibitor proteins from persons with hereditary angioneurotic edema with respect to each of the enzymes regulated by normal C1-inhibitor. To do this, fragments of normal C1-inhibitor generated with cyanogen bromide, or by limited proteolytic digestion, will be examined for their inhibitory activity and their ability to form complexes-with these proteases (factor Xlla, kallikrein, plasmin, C1s. 2. There are multiple possible explanations for altered expression of the C1-inhibitor gene in hereditary angioneurotic edema. One approach to be used in this laboratory to gain insights into this problem will be to compare mRNA from peripheral blood monocytes of normal persons to that from persons with different types of hereditary angioneurotic edema. Both the quantity and quality of mRNA from these patients will be compared to that from normal individuals. 3. Cultured human umbilical endothelial cells will be tested for antigens located on the heavy or light chains of human high molecular weight kininogen. Since light chain participates in binding to certain substances and in generating clot-promoting activity, it might be identified on endothelial membranes, and might transfer to these cells under definable states in which its function would be provoked. Additional studies will examine the ratios of plasma concentrations of light and heavy chain antigens of HMWK in plasma from normal persons- and those with pathologic states involving the vasculature.