CELL MATRIX INTERACTIONS OF LUNG TISSUE

肺组织细胞基质相互作用

• 批准号: 3343035
• 负责人: MARVIN L TANZER
• 金额: $ 11.86万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-09-30 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3343035
• 关键词: alveolar macrophages; animal age group; animal old age; cell age; cell cell interaction; cell differentiation; cell fusion; cell type; connective tissue development; density gradient ultracentrifugation; embryo /fetus cell /tissue; extracellular matrix; fibroblasts; lung alveolus; membrane fusion; mixed tissue /cell culture; monoclonal antibody; pulmonary fibrosis /granuloma; radioimmunoassay; reagent /indicator; respiratory epithelium; scintillation counter; spectrometry

The mammalian lung contains a number of cell types and subtypes surrounded and supported by extracellular matrices, either interstitial or basement membrane in nature. Such matrices contain collagen, elastin, proteoglycans, fibronectin, and other macromolecular components; the integrity of the matrix is thought to account for many of the mechanical properties of lung. In pulmonary diseases, the matrix is often prominently affected. For example, in emphysema, derangement of elastin occurs so that it is morphologically abnormal; type II cell proliferation and differentiation may be influenced by exposed basement membranes during lung repair. We propose to address questions of matrix production and cell-matrix interactions in normal and fibrotic lung, using a cell culture approach. Three major protocols are: 1) to elucidate, in detail, the biogenesis of matrix macromolecules as a function of chronologic age, from embryonic lung to senescent lung; the appearance and temporal sequence of specific marcomolecules elaborated by lung fibroblasts will be quantitatively assayed; 2) to develop pure populations of type II alveolar cells, endothelial cells from capillary (alveolar) regions and pulmonary artery, and to define the abilities of these cells to maintain their differentiated state on preformed matrices, as well as the capability of the cells to produce specific matrix components; the ability of specific cell membrane components to recognize matrix molecules. These studies will rely upon development of monoclonal antibodies for specific cell selection and for cell-matrix interactions; 3) to study the effects of disease processes upon control of lung cell proliferation and production of matrix components; the role of factors elaborated by mononuclear cells of fibrotic lung in regulating matrix production of pure cell populations will be examined, using co-culture or conditioned media. This integrated approach should help define the relationships between certain alveolar cell types and their supporting extracellular matrix, both in normal lung and in a model of pulmonary fibrosis. Insights into the cell-matrix interactions may be forthcoming when reagents such as monoclonal antibodies are used to dissect the cells from the matrix with the aim of identifying specific cell membrane binding sites, similar to those described in non-pulmonary tissues.

哺乳动物的肺包含许多细胞类型和亚型， 并由细胞外基质支持，无论是间质还是基底 自然界中的膜 这种基质含有胶原蛋白，弹性蛋白， 蛋白聚糖、纤连蛋白和其他大分子组分; 基质的完整性被认为是许多机械 肺的性质。 在肺部疾病中，基质往往很突出 影响。 例如，在肺气肿中，弹性蛋白发生紊乱， 它是形态异常的; II型细胞增殖， 分化可能受到肺发育过程中暴露的基底膜的影响， 修复. 我们建议解决矩阵生产的问题， 正常肺和纤维化肺的细胞-基质相互作用，使用细胞培养 approach. 三个主要协议是：1）详细阐明 基质大分子的生物发生作为年龄的函数， 胚胎肺到衰老肺的形态和时序 由肺成纤维细胞加工的特异性大分子将被 定量分析; 2）开发II型肺泡上皮细胞的纯群体 细胞，毛细血管（肺泡）区域和肺的内皮细胞 动脉，并确定这些细胞的能力，以维持其 预成型矩阵上的微分状态，以及 细胞产生特异性基质成分的能力;特异性 细胞膜成分识别基质分子。 这些研究将 依赖于单克隆抗体的发展， 和细胞-基质相互作用; 3）研究疾病的影响 控制肺细胞增殖和基质产生的方法 成分;纤维化的单核细胞阐述的因素的作用 肺在调节纯细胞群基质产生中的作用将是 使用共培养物或条件培养基检查。 这一综合办法 应该有助于定义某些肺泡细胞类型之间的关系 和它们的支持细胞外基质，无论是在正常的肺和在一个 肺纤维化模型。 深入了解细胞-基质相互作用 当诸如单克隆抗体的试剂用于 从基质中解剖细胞，目的是识别特定细胞 膜结合位点，类似于非肺组织中描述的那些。