INFLUENCE OF FIBROBLASTS UPON TYPE II CELL MATURATION

在妊娠后期，肺部发生了显著的变化。 为其向充液状态的转变做准备。最多的 值得注意和重要的事件是表面活性剂体系的出现。 有证据表明，几种荷尔蒙可能参与决定 最后的成熟过程。最近的证据表明， 成纤维细胞-肺泡细胞因子可能在血管内皮细胞的增殖中发挥作用 II型细胞对皮质醇的反应。目前尚不清楚FPF是如何作用于 II型细胞，哪些其他激素可以通过FPF引起它们的影响，或者 在II型细胞的不同系统上，FPF可能有多普遍。这个 本申请将利用两种不同的培养胎儿的系统 类型II细胞为了确定FPF可能的相互关系， 糖皮质激素、T3和胰岛素对表面活性物质产生的影响。其中一个系统是 含有90%以上浓缩物的原代单层培养物 在II型细胞中。第二个系统包含聚集的II型细胞 (器官类型的)培养，细胞在体内保持类似的形状， 细胞之间的接触，并在体外几周内稳定。这些 两个系统有很大的不同，因此可以预期它们可能 对外生因素有不同的反应。因此，他们是极好的一对 以研究FPF的影响有多普遍。会是 已确定fpf是否增强了对这些区域性的响应 地塞米松和T_3以及T_3或胰岛素是否通过 成纤维细胞。通过使用几种不同的同位素，测定其活性 脂肪合成酶及不同水池大小的测定 磷脂酰胆碱将确定FPF如何作用于II型 手机。确定FPF是否影响表面活性物质的分泌或类型 II细胞的生长也会有所进展。这是一个次要的目标 应用是肺成纤维细胞产生的抑制因子 表面活性剂合成。将确定是胰岛素还是高胰岛素 葡萄糖浓度会影响抑制剂的生产。这是 之所以重要，是因为糖尿病母亲的婴儿发病率增加 呼吸窘迫综合症。抑制剂的作用机制 对II型细胞的影响也将被研究。

The lung undergoes marked alterations during the latter part of gestation in preparation for its transition to a fluid filled state. The most notable and important event is the appearance of the surfactant system. There is evidence that several hormones may be involved in determining the final maturation process. Recent evidence suggests that a fibroblast-pneumocyte factor (FPF) may play a role in amplication of the response of type II cells to cortisol. It is not known how FPF acts upon the type II cell, what other hormones may elicit their effect via FPF, or how universal the FPF may be on different systems of type II cells. The present application will utilize two different systems of culturing fetal type II cells in order to determine the possible interrelationships of FPF, glucocorticoids, T3 and insulin upon surfactant production. One system is a primary monolayer culture containing a greater than 90 percent enrichment in type II cells. The second system contains type II cells in aggregate (organotypic) culture where the cells maintain an in vivo like shape, cell-to-cell contacts, and are stable for several weeks in vitro. These two systems are sufficiently different so as to expect that they may respond to exogenous factors differently. Thus they make an excellent pair of systems to study how universal the effect of FPF is. It will be determined whether FPF augments the response to these cultures to dexamethasone and T3 and whether T3 or insulin affect production of FPF by fibroblasts. By use of several different isotopes, assay of activities of lipid synthesizing enzymes, and measurement of pool sizes of different phosphatidylcholines it will be determined how FPF acts upon the type II cell. A determination of whether FPF affects suriactant secretion or type II cell growth will also be made. A secondary objective of this application is the factor produced by lung fibroblasts which inhibits surfactant synthesis. It will be determined whether insulin or high glucose concentrations affect production of the inhibitors. This is of importance because infants of diabetic mothers have an increased incidence of respiratory distress syndrome. The mechanism by which the inhibitor affects the type II cell will also be studied.