TYPE II CELLS AND INTERSTITIAL LUNG DISEASE

II 型细胞和间质性肺疾病

• 批准号: 3736273
• 负责人: ROBERT J MASON
• 金额: --
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3736273
• 关键词: cell cell interaction; cell differentiation; cellular pathology; collagen; cytokine; cytoskeleton; disease /disorder model; extracellular matrix; fibronectins; gene expression; genetic regulation; genetic transcription; human tissue; hyperplasia; immunocytochemistry; laboratory rat; laminin; macrophage; pathologic process; phospholipids; proteoglycan; pulmonary fibrosis /granuloma; pulmonary surfactants; respiratory epithelium; tissue /cell culture

Alveolar type II cells are specialized epithelial cells that line the alveolus and synthesize and secrete pulmonary surface active material. In interstitial lung disease (ILD) with extensive alveolar pathology, the composition of surface active material is abnormal which may contribute to the increased elastic recoil, alveolar collapse and fibrosis in ILD. Type II cells are also the progenitor cells for the epithelium, and proliferation of type II cells is thought to be critical for the restoration of gas exchange units after alveolar injury. This project is based on the hypotheses that type II cells are intimately involved in the pathogenesis of ILD and that the hypertrophic type II cells characteristic of ILD are functionally different from the type II cells of normal lung. The regulation of differentiated function by normal type II cells is just beginning to be understood, and we must know about normal cells before we can understand hypertrophic type II cells. We will determine the role of extracellular matrix, cytoskeletal architecture, and cell-cell interactions on the maintenance of differentiated function of normal type II cells. The importance of lung derived extracellular matrix from normal and injured lung on type II cell differentiation will be tested. Differentiated function will be assessed by transcriptional and post-transcriptional regulation of the genes for the surfactant proteins SP-A, SP-B, and SP-C and the synthesis of surfactant phospholipids. We will use immunocytochemical techniques to detect incorporated bromodeoxyuridine and proliferating cell nuclear antigen (PCNA) to demonstrate that the term "type II cell hyperplasia" describes an increase in the number of hypertrophic type II cells, only a subset of which are actually proliferating and the rest we believe are arrested in an altered state of differentiation. We will determine if the hypertrophic type II cells are synthesizing and secreting an abnormal surfactant low in phosphatidylglycerol and surfactant protein A. We will also establish if they are secreting cytokines that influence other type II cells, mesenchymal cells, or macrophages. These studies will demonstrate the importance of type II cells in the pathogenesis of ILD.

肺泡 II 型细胞是排列在肺泡上的特殊上皮细胞 肺泡合成和分泌肺表面活性物质。 在 具有广泛肺泡病变的间质性肺疾病 (ILD) 表面活性物质的成分异常可能会导致 ILD 中弹性回缩增加、肺泡塌陷和纤维化。 类型 II 细胞也是上皮的祖细胞，并且 II 型细胞的增殖被认为对于 肺泡损伤后气体交换单位的恢复。 这个项目是 基于 II 型细胞密切参与的假设 ILD 的发病机制和肥大的 II 型细胞特征 ILD 的功能与正常肺的 II 型细胞不同。 正常II型细胞对分化功能的调节只是 开始被理解，我们必须先了解正常细胞 可以了解肥大的II型细胞。 我们将确定角色 细胞外基质、细胞骨架结构和细胞间相互作用 维持正常II型细胞的分化功能。 这 正常和受损肺源性细胞外基质的重要性 肺对II型细胞分化的影响将被测试。 差异化 功能将通过转录和转录后评估 表面活性蛋白 SP-A、SP-B 和 SP-C 基因的调控 以及表面活性剂磷脂的合成。 我们将使用 免疫细胞化学技术检测掺入的溴脱氧尿苷和 增殖细胞核抗原（PCNA）来证明该术语 “II型细胞增生”描述的是细胞数量的增加。 肥大的 II 型细胞，实际上只有其中的一个子集 扩散，而我们认为其余的都在改变的状态下被逮捕 差异化。 我们将确定肥大的 II 型细胞是否是 合成和分泌异常表面活性剂含量低 磷脂酰甘油和表面活性蛋白 A。我们还将确定是否 它们正在分泌影响其他 II 型细胞的细胞因子， 间充质细胞或巨噬细胞。 这些研究将证明 II 型细胞在 ILD 发病机制中的重要性。