REGULATION OF PROTEOLYSIS IN LUNG TISSUE

目前提案的目标是继续调查 蛋白酶抑制剂及其靶酶在发育中的作用 肺部疾病。 重点将放在确定以下方面的贡献： 肺上皮细胞合成分泌功能急性期 蛋白酶抑制剂，用于防御组织蛋白水解， 由嗜中性粒细胞衍生的蛋白酶的器官。 在这方面，具体 补助金的目的涉及a）对财产的调查 上皮细胞衍生的抑制剂，和B）评估对 上皮细胞的各种细胞因子，这些细胞因子已知刺激急性 相蛋白质合成。 因为肺部很容易被感染， 各种细菌和真菌有机体，其中许多可以释放其 c）还计划了自身的、不受控制的蛋白水解活性的实验 以检查急性期或急性期细胞因子的稳定性， 蛋白质合成或中性粒细胞趋化性，治疗后， 宿主蛋白酶和d）确定这些酶是否也可以降解 特异性靶细胞上的细胞因子和趋化因子受体。 所有 这些结果应该提供重要的信息， 合成的蛋白酶抑制剂确实有助于肺防御 不受控制的蛋白质水解宿主衍生的酶。 此外，重要的 将获得关于宿主和非宿主的能力的数据 蛋白酶通过以下途径失调细胞间通讯 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.