TYPE II CELLS AND INTERSTITIAL LUNG DISEASE

II 型细胞和间质性肺疾病

• 批准号: 3758234
• 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/3758234
• 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内的特化上皮细胞