THROMBIN IN WOUND HEALING--MULTIPLE FUNCTIONS

凝血酶，一种调节性胰蛋白酶样丝氨酸蛋白酶，被公认为 它在凝血中的主要作用，已经被证明有 伤口愈合过程中附加功能的潜力(S)。 凝血酶的其他建议功能包括：1)直接调节 血管流动；2)巨噬细胞的趋化活性，也许， 中性粒细胞；3)成纤维细胞的有丝分裂活性。更有甚者 凝血酶从血小板释放的物质，如凝血酶反应蛋白和 血小板衍生生长因子在创伤愈合中的重要作用 进程。因此，除了两个基本的反应之外， 保护血管的完整性，纤维蛋白原的凝结和 凝血酶在血小板聚集中具有广泛而多样的作用。 伤口愈合过程。 本提案所述研究的重点是 对这些不同活动的结构关系的研究。 特别是有限的蛋白质分解和特定化学物质的组合 修饰性将被用来研究结构之间的关系 与人凝血酶相互作用特异的决定因素 纤维蛋白原、纤维蛋白、血小板、血栓调节蛋白和凝血酶原片段2。 影响凝血酶对纤维蛋白吸附及后续吸收的因素 平衡释放将被阐明。研究的这一部分是 尤其重要的是检验凝血酶是 由纤维蛋白和伤口部位浓缩而成，便于后续愈合过程。 中性粒细胞和巨噬细胞在伤口愈合和 将进行研究以确定纤维蛋白结合凝血酶 保持趋化活性。最后，从血小板中释放的物质 将评估其在凝血过程中的定量影响(S) 凝血酶的生物调节作用。从这些研究中获得的结果 研究将允许更合理地发展增强因素 正常和受损个体的伤口愈合。

Thrombin, a regulatory tryptic-like serine protease, well recognized for its cardinal function in blood coagulation, has been demonstrated to have the potential for additional function(s) in the wound-healing process. Other suggested functions for thrombin include 1) direct mediation of vascular flow; 2) chemotactic activity for macrophages and, perhaps, neutrophils and 3) mitogenic activity for fibroblasts. Furthermore materials released from platelets by thrombin, such as thrombospondin and platelet-derived growth factor, play an important role in the would-healing process. Thus, beyond the two basic reactions fundamental for the preservation of vascular integrity, the clotting of fibrinogen and aggregation of platelets, thrombin has a broad and diverse role in the wound healing process. The focus on the research described in the present proposal is directed at the study of the structural relationships of these various activities. Specifically a combination of limited proteolysis and specific chemical modification will be used to study the relationship of structural determinants on human thrombin which are specific for interaction with fibrinogen, fibrin, platelets, thrombomodulin and prothrombin fragment 2. Factors influencing the absorption of thrombin to fibrin and subsequent equilibrium release will be elucidated. This portion of the study is of particular importance in the testing of the hypothesis that thrombin is concentrated by fibrin and the wound-site for subsequent healing process. Neutrophils and macrophages are of critical importance in wound-healing and studies will be performed to determine whether fibrin-bound thrombin retains chemotactic activity. Finally, material released from platelets during coagulation will be evaluated for their quantitative effect(s) on the bioregulatory action of thrombin. The results obtained from these studies will permit the more rationale development of enhancing factors for wound-healing in normal and compromised individuals.