TYPE 11 PNEUMOCYTE-EXTRACELLULAR MATRIX INTERACTIONS

正常肺泡上皮表面主要由扁平的 I型肺细胞，一种对损伤非常敏感的细胞， 较小程度的立方形II型细胞。 II型肺细胞通常 一种非增殖性细胞，但当肺受伤时，如成年人， 呼吸窘迫综合征或特发性肺纤维化，II型 细胞增殖并排列在肺泡表面的大部分。 对于正常 要恢复结构，增生的II型细胞必须 分化成扁平的I型细胞。 II型细胞的控制 增殖和分化还没有被很好地理解。 的功能和 许多上皮细胞的形态受到基底膜的影响 和细胞外基质。 我们建议研究如何 细胞外基质影响对II型细胞的增殖反应 并分化为I型肺细胞。 将从大鼠中分离II型细胞，并通过 磷脂组合物、抗表面活性剂抗体结合，以及 在电子显微镜下观察到的片状体。 这些细胞将在 在具有完整基底膜的脱细胞人羊膜上培养 另一侧为暴露的间质基质。 它是已知的 如评估的，当在两侧生长时，II型细胞的形态不同 通过光学、扫描和透射电子显微镜。 我们将评估 增殖的细胞在每一侧的羊膜由氚 胸苷掺入、细胞数计数和放射自显影。 的 细胞的分化将通过测定它们的 凝集素结合谱。 II型细胞的功能将通过 它们的磷脂和基质分泌。 此外，研究II型细胞形态，增殖， 分化和功能将在膜上生长期间完成 先前被激活的多形核白细胞破坏。 其他因素，如支气管肺泡灌洗液（BAL），将进行测试 用于刺激培养物中的II型细胞增殖。 BAL液来自 将正常志愿者与肺结核患者进行比较， 其中存在II型细胞增生的疾病。 这种方法应该增加我们对控制II型糖尿病的理解。 细胞增殖和分化以及基质在其中的作用 确定肺泡损伤的修复。 新技术将 包括肺泡II型细胞在体外受损基质上生长， I型和II型细胞的详细凝集素结合分析。

The normal alveolar epithelial surface is covered predominantly by flat Type I pneumocytes, a cell which is very sensitive to injury, and to a lesser extent by cuboidal Type II cells. The Type II pneumocyte is usually a non-proliferative cell, but when the lung is injured, as in adult respiratory distress syndrome or idiopathic pulmonary fibrosis, the Type II cell proliferates and lines much of the alveolar surface. For a normal architecture to be restored, the hyperplastic Type II cells must differentiate into flat Type I cells. The control of Type II cell proliferation and differentiation is not well understood. The function and morphology of many epithelial cells are influenced by the basement membrane and extracellular matrix on which they rest. We propose to study show how extracellular matrix influences the proliferative response to Type II cells and their differentiation into Type I pneumocytes. Type II cells will be isolated from rats and identity confirmed by phospholipid composition, antisurfactant antibody binding, and the presence of lamaellar bodies on electron microscopy. The cells will be grown in culture on an acellular human amnion with intact basement membrane on one side and exposed interstitial stroma on the other. It is known that the morphology of Type II cells differs when grown on the two sides as assessed by light and scanning and transmission electron microscopy. We will assess proliferation of the cells on each side of the amnion by tritiated thymidine incorporation, counting of cell number and autoradiography. The differentiation of the cells will be probed by determination of their lectin binding profile. Function of the Type II cells will be assessed by their phospholipid and matrix secretion. In addition, studies of Type II cell morphology, proliferation, differentiation and function will be done during growth on a membrane previously damaged by activated polymorphonuclear leukocytes. Other factors, such as bronchoalveolar lavage (BAL) fluid, will be tested for stimulation of Type II cell proliferation in culture. BAL fluid from normal volunteers will be compared with that form patients with pulmonary diseases in which there is Type II cell hyperplasia. This approach should increase our understanding of the control of Type II cell proliferation and differentiation and of the role of the matrix in determining the repair of alveolar injury. New technologies used will include growth of alveolar Type II cells on an in vitro damaged matrix and detailed lectin binding analysis of Type I and II cells.