CHEMICAL MEDIATORS OF ACUTE PULMONARY DISORDERS

这一合作努力的主要目标仍然是 用生物化学和功能术语表征某些细胞， 被认为与支气管哮喘有关的化学介质。 细胞特异性蛋白质的表征和特异性抗体的开发 cDNA探针将允许研究小鼠肥大细胞的调节 表型在体外和体内。 关于联合国系统作用的相关研究 成纤维细胞在决定肥大细胞在相关增殖 的成纤维细胞将作为体外研究的背景， 肺纤维化小鼠模型。 正常和肥大的研究 细胞缺陷品系的小鼠将利用肥大细胞特异性探针 在免疫化学和杂交分析中确定肥大细胞 正常和重组肥大细胞缺陷型肺表型 与肺机械评估相关的应变 在体内对IgE依赖性肥大细胞活化的应答。 肥大细胞 在包括肺在内各种人体组织中， 通过可用技术进行免疫化学表征， 用基因特异性cDNA探针定义推定的表型， 后者变得可用。 人类肥大细胞的体外研究将使用 逆转录病毒技术，建立永生细胞系作为来源， 用于开发肥大细胞特异性探针的cDNA文库， 体外和体内人肥大细胞的表征。 配套 人嗜酸性粒细胞的体外研究将集中在分离 LTC4合酶的结构表征和克隆， 从LTA4和谷胱甘肽形成LTC4，并且在进一步定义LTC4时， 特异性细胞因子在维持细胞有丝分裂后活力中的作用 人嗜酸性粒细胞和增强其激动剂引发的形成， LTC4的发布 LTC4的靶细胞功能，无论是直接还是通过 转化为LTD4，将在体外和体内进一步分析， 动物系统以及正常和哮喘患者。 的关系 在气道反应性中，深吸气对气道的影响 口径，以及肺部和气道的炎症状态， 介质、细胞类型和微血管通透性的测量 将用于哮喘患者的评估。

The major objective of this collaborative effort continues to be to characterize in biochemical and functional terms certain cells and chemical mediators considered to be involved in bronchial asthma. Characterization of cell-specific proteins and development of specific cDNA probes will allow studies of the regulation of murine mast cells phenotypes in vitro and in vivo. Companion studies of the role of the fibroblast in determining the mast cell in the associated proliferation of the fibroblasts will serve as the background for in vitro studies of pulmonary fibrosis in a mouse model. The studies of normal and mast cell-deficient strains of mice will utilize the mast cell-specific probes in immunochemical and hybridization analyses to define mast cell phenotypes in lung of normal and reconstituted mast cell-deficient strains in association with the assessment of the pulmonary mechanical response to IgE-dependent mast cell activation in vivo. The mast cells in various human tissues, including lung, require ultrastructural and immunochemical characterization by available techniques with further definition of putative phenotypes with gene-specific cDNA probes as the latter become available. In vitro studies of human mast cells will use retrovirus technology to establish immortalized cell lines as a source of a cDNA library for development of mast cell-specific probes for characterization of human mast cells in vitro and in vivo. The companion in vitro studies of human eosinophils will focus on the isolation structural characterization and cloning of the enzyme LTC4 synthase which forms LTC4 from LTA4 and glutathione and on the further definition of the role of specific cytokines in maintaining the post-mitotic viability of human eosinophils and in augmenting their agonist-initiated formation and release of LTC4. The target cell function of LTC4, whether direct or via conversion to LTD4, will be further analyzed in vitro and in vivo in animal systems and in normal and asthmatic humans. The relationships among airway responsiveness, the effects of a deep inhalation on airway caliber, and the inflammatory state of the lungs and airways based on measurements of mediators, cell types, and microvascular permeability will be assessed for asthmatic humans.