TYPE 11 PNEUMOCYTE-EXTRACELLULAR MATRIX INTERACTIONS

正常肺泡上皮表面主要被扁平覆盖。 I型肺泡细胞是一种对损伤非常敏感的细胞，对 面积较小的为立方II型细胞。II型肺泡细胞通常是 一种非增殖性细胞，但当肺损伤时，如成人 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区域。对于一个正常的 要修复结构，增生型II型细胞必须 分化为扁平的I型细胞。II型细胞的控制 增殖和分化还不是很清楚。功能和 许多上皮细胞的形态受到基底膜的影响 以及它们赖以生存的细胞外基质。我们打算研究展示如何 细胞外基质对II型细胞增殖反应的影响 分化为I型肺泡细胞。 将从大鼠身上分离出II型细胞，并通过 磷脂组合物，抗表面活性抗体结合，以及存在 在电子显微镜下观察板层小体。这些细胞将在 基底膜完整的脱细胞人羊膜的培养 另一侧为裸露的间质间质。据了解， 根据评估，当生长在两侧时，II型细胞的形态不同 通过光学、扫描和透射电子显微镜观察。我们将评估 氚对羊膜两侧细胞增殖的影响 胸腺嘧啶核苷掺入、细胞计数和放射自显影。这个 细胞的分化将通过测定它们的数量来进行。 凝集素结合图谱。第二类细胞的功能将通过以下方式进行评估 它们的磷脂和基质分泌。 此外，对II型细胞的形态、增殖、 分化和功能是在膜上生长的过程中进行的 先前被激活的中性粒细胞损伤。 其他因素，如支气管肺泡灌洗液(BAL)，将进行测试 用于刺激培养中的II型细胞增殖。BALL流体来自 将正常志愿者与肺部疾病患者进行比较 有II型细胞增生的疾病。 这种方法应该会增加我们对第二类控制的理解 细胞的增殖和分化以及基质在其中的作用 确定牙槽骨损伤的修复方法。使用的新技术将 包括肺泡II型细胞在体外受损基质上生长，以及 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.