HUMAN TISSUE FACTOR AND ITS PLASMA INHIBITOR

凝血因子VII-组织启动凝血的实验研究 因子途径不仅对正常止血很重要，而且 可能在病理性血栓形成中也起到了作用。蜂窝 组织因子的表达与感染性、炎症性、 和肿瘤疾病，并可能在一定程度上负责 血栓栓塞症不仅是这些疾病的并发症，也是 静脉血栓栓塞症和肺栓塞症 其他正常的人也是如此。 血浆中含有VII-Tf复合体的内源性抑制物 我们给拉奇打电话。它与血浆中的脂蛋白和 需要Xa的存在来表达其反馈抑制 VII-Tf。 我们计划通过分离LacI的cDNA来进一步鉴定LacI， 测定其抑制酶的光谱和动力学， 并研究了LacI的结构和功能关系 分子与脂蛋白的结合，其 Xa的抑制作用及其与植物体内其他成分的关系 可能的VII-Tf-Xa-LaCI抑制复合体。其他研究 还将研究细胞合成Tf和Laci的情况， 正常人组织中Tf/LacI的免疫组织化学定位 和病理组织，并评估组织因子之间的关系 Laci血药浓度与临床疾病的关系。 这些研究将使用纯化的Tf和LaCI进行， 通过蛋白质分解或化学处理产生的片段 (CnBR)，它们分离的cDNA，基于它们的合成肽 预测的氨基酸序列，以及适当的克隆和 多克隆抗体。 这些实验旨在提供目前缺乏的信息， 关于凝血的引发和控制以及 古典“外在”与“内在”的相互关系 小路。这一结果应该会加深我们对两者的理解 正常止血和病理性血栓栓塞症。

The initiation of blood coagulation through the factor VII-Tissue Factor pathway is not only important for normal hemostasis, but likely plays a role in pathological thrombosis as well. Cellular expression of TF has been correlated with infectious, inflammatory, and neoplastic disease, and may be responsible in part for the thromboembolic complications of not only these illnesses, but also the venous thromboembolic and pulmonary embolism occurring in otherwise normal individuals as well. Plasma contains an endogenous inhibitor of the VII-TF complex which we call LACI. It is associated with the lipoproteins in plasma and requires the presence of Xa to express its feedback inhibition of VII-TF. We plan to further characterize LACI by isolating its cDNA, determining the spectrum and kinetics of its protease inhibition, and investigating the structure function relationships of the LACI molecule vis a vis its association with lipoproteins, its inhibition of Xa, and its relationship to the other components in the putative VII-TF-Xa-LACI inhibitory complex. Additional studies will also investigate the synthesis of TF and LACI by cells, determine the immunohistochemical localization of TF/LACI in normal and pathological tissues, and assess the relationship between TF and LACI blood concentrations and clinical disease. These studies will be performed using purified TF and LACI, fragments of them produced by proteolysis or chemical treatment (CnBr), their isolated cDNAs, synthetic peptides based on their predicted amino acid sequence, and appropriate monoclonal and polyclonal antibodies. The experiments are designed to provide information, now lacking, concerning the initiation and control of coagulation and the interrelationship between the classical "extrinsic" and "intrinsic" pathways. The results should enhance our understanding of both normal hemostasis and pathologic thromboembolism.