REGULATION OF PROTEOLYSIS IN LUNG TISSUE

目前提案的目标是继续调查 蛋白水解酶抑制剂及其靶酶在发育中的作用 肺部疾病。重点是确定以下方面的贡献 肺上皮细胞合成分泌功能急性期 用于防御组织蛋白分解的蛋白酶抑制剂通过 器官通过中性粒细胞衍生的蛋白水解酶。在这方面，具体的 赠款的目的包括a)调查 上皮细胞衍生的抑制物和b)对 各种细胞因子的上皮细胞，已知能刺激急性 时相蛋白质合成。因为肺部很容易被一种 各种细菌和真菌生物体，其中许多可以释放它们的 自己的，不受控制的蛋白分解活动，实验也计划c) 来检测两个急性期的细胞因子的稳定性 蛋白质合成或在中性粒细胞趋化作用中，用非 宿主蛋白水解酶和d)确定这些酶是否也能降解 特定靶细胞上的细胞因子和趋化因子受体。所有的 这些结果应该会给出重要的信息，说明当地 合成的蛋白水解酶抑制剂确实有助于肺防御 由宿主衍生的酶不受控制的蛋白质分解。此外，重要的是 将获得有关主机和非主机的能力的数据 蛋白水解酶通过以下两种途径之一失调细胞间的通讯 细胞因子或受体降解。

The goals of the current proposal are to continue investigations into the role of proteinase inhibitors and their target enzymes in the development of lung disease. Focus will be made on determining the contribution of lung epithelial cells in synthesizing and secreting functional acute phase proteinase inhibitors for defense against tissue proteolysis in this by organ by neutrophil-derived proteinases. In this context, the specific aims of the grant involve a) an investigation of the properties of the epithelial cell-derived inhibitors and b) assessment of the effect on epithelial cells of various cytokines which are known to stimulate acute phase protein synthesis. Because the lung can easily be infected by a variety of bacterial and fungal organisms, many of which can release their own, uncontrolled proteolytic activities, experiments are also planned c) to examine the stability of cytokines involved in either acute phase protein synthesis or in neutrophil chemotaxis, after- treatment with non- host proteinases and d) to determine whether such enzymes can also degrade receptors for cytokines and chemotaxins on specific target cells. All of these results should give significant information as to whether locally synthesized proteinase inhibitors do contribute to lung defense against uncontrolled proteolysis by host-derived enzymes. In addition, important data will be obtained regarding the ability of host and non-host proteinases to dysregulate cell to cell communication through either cytokine or receptor degradation.