REGULATION OF ACID/BASE TRANSPORT IN ALVEOLAR EPITHELIUM

肺泡上皮细胞（AEC）覆盖肺的肺泡表面， 它是哺乳动物的主要排酸器官。因为这些细胞 在pCO 2方面，受到不恒定的细胞外环境的影响， 肺泡上皮细胞中细胞内pH（pHi）的调节是 具有特殊意义。在以前的工作中已经确定， 肺泡细胞pHi受几种离子转运机制调节 其能够影响酸/碱进入或从细胞中排出。 这些离子转运机制是质膜蛋白不对称 分布在极化的上皮细胞表面， 可能的酸/碱当量的跨上皮转运。他们的 跨肺泡的膜极性分布 上皮细胞，其顶端衬里液pH为酸性（6.9）， 以前建立的。我们将研究 AEC的酸/碱转运通过研究三个假设来调节：（1） AEC通过特定的离子转运机制进行酸/碱转运 具有关于膜极性的特征分布 代表了特定运输的活性 蛋白质异构体。(2)这些离子传输机制都是急性的， 在AEC中就活性、表达和 通过特定的细胞外刺激， 在正常条件下和疾病状态下的酸/碱转运。（三） AEC中酸碱转运机制的调控与定位 影响肺泡液pH值。本文提出的研究目的 因此，进一步表征酸/碱转运机制 在原子能委员会中，特别是研究其活动调节， 表达和极性的特异性外源性因素和肺损伤。我们 将使用大鼠肺泡上皮细胞单层培养的组织 培养物处理的聚碳酸酯过滤器用于许多这些研究。这 该模型特别适合于肺泡上皮细胞的研究 极性和酸/碱运输。我们将验证我们的研究结果使用在 大鼠肺泡上皮的原位研究。这一长期目标 项目是为了确定酸/碱运输的重要性， 肺泡上皮细胞的细胞内稳态，并证明 肺泡上皮细胞酸/碱转运在调节细胞凋亡中作用 细胞外肺泡环境。

Alveolar epithelial cells (AEC) cover the alveolar surface of the lung, which is the major acid-excreting organ in mammals. Because these cells are subject to an inconstant extracellular milieu with respect to pCO2, the regulation of intracellular pH (pHi) in alveolar epithelial cells is of particular significance. In previous work it has been established that alveolar pneumocyte pHi is regulated by several ion transport mechanisms that are capable of effecting acid/base entry or extrusion from the cell. These ion transport mechanisms are plasma membrane proteins asymmetrically distributed across polarized epithelial cell surfaces, thereby making transepithelial transport of acid/base equivalents possible. Their distribution with respect to membrane polarity across the alveolar epithelium, whose apical lining fluid pH is acidic (6.9), has not previously been established. We will investigate the mechanisms whereby acid/base transport by AEC is regulated by studying three hypotheses: (1) Acid/base transport by AEC occurs via specific ion transport mechanisms having a characteristic distribution with respect to membrane polarity across the cells, and which represent the activity of specific transport protein isoforms. (2) These ion transport mechanisms are both acutely and chronically regulable in AEC with respect to activity, expression, and polarity by specific extracellular stimuli that can thereby modulate acid/base transport under normal conditions and in disease states. (3) Regulation and localization of acid/base transport mechanisms in AEC influence alveolar fluid pH. The objectives of the studies proposed herein are therefore to further characterize the acid/base transport mechanisms in AEC, and in particular, to study regulation of their activity, expression, and polarity by specific exogenous factors and lung injury. We will use rat alveolar epithelial cell monolayers cultured on tissue culture-treated polycarbonate filters for many of these studies. This model is especially well suited for studies on alveolar epithelial polarity and acid/base transport. We will validate our findings using in situ studies on rat alveolar epithelium. The long term goals of this project are to define the importance of acid/base transport in intracellular homeostasis of alveolar epithelial cells, and to demonstrate the role of acid/base transport by alveolar epithelial cells in modulation of the extracellular alveolar milieu.