TEAR GLAND FLUID FORMATION

本项目将重点研究质膜的胞内运输。 兔泪腺分离的腺泡细胞的化学成分。这个 泪腺是伺服机构中的效应器，有助于 保持眼表健康，泪水不足 功能会导致痛苦的干眼症。泪腺功能不全可 由荷尔蒙紊乱或局部自身免疫现象引起。 尤其迫切的是，导致自身免疫的机制 泪液不足是可以理解的。这种现象经常是 伴有自身免疫性唾液腺功能障碍，严重 对口腔健康和许多系统性疾病的后果 至少部分是由免疫复合体沉积引发的。这些 干燥综合征的症状特征是影响到不止一个 百万55岁以上的美国女性。 最近的亚细胞分离和形态研究表明 Na、K-ATPase等腺泡细胞质膜蛋白参与 在往返于胞内池的大量回收流量中， 它似乎被组织成早期和晚期的内吞细胞室。 分离机制似乎允许在 两个隔室，但允许Na，K-ATPase从晚期到 早期脑室仅对胆碱能刺激有反应。过份 刺激似乎改变了晚期的微域组织 并削弱其参与细胞内的能力 流动相交通。如此广泛的偷偷者的存在- 受控的小区内流量表明了一种可行的假设，即 腺泡细胞通过发挥功能触发局部自身免疫反应 类似于特化的抗原提呈细胞。初步数据 确认腺泡细胞含有潜在的免疫原性蛋白(Lg- AG2)，并且它们可以表示机器的几个部件 抗原提呈，包括组织蛋白酶B，这可能会切除 免疫原肽片段和第二类组织相容性分子， 它可能会结合免疫原性片段，并将它们展示给T细胞。它 也有可能是泪腺中出现了额外的多肽 间质可为T细胞活化提供辅助信号。这个 拟议研究的具体目标是：1)描述和调查 内吞胞体早期和晚期的微域组织 车厢。2)确定负责重新组织 最佳胆碱能和过量胆碱能引起的晚期内吞间隔 刺激。3)绘制组织蛋白B和组织蛋白B的亚细胞分布图 D、LG-AG2和II类组织相容性分子 它们可以在与血浆沟通的隔间中蓄积 薄膜。如果该项目探索的假设被证明是正确的， 那么，对事件的理解就会取得进展 膜转运蛋白的基本插入和回收，以及 将为了解腺泡细胞激活T细胞的尝试设定阶段 细胞。

This project will focus on the intracellular traffic of plasma membrane constituents in acinar cells isolated from rabbit lacrimal glands. The lacrimal glands are effector organs in a servomechanism that helps maintain the health of the ocular surface, and insufficient lacrimal function leads to painful dry eye conditions. Lacrimal insufficiency can result from hormonal perturbations or from local autoimmune phenomena. It is particularly urgent that the mechanisms leading to autoimmune lacrimal insufficiency be understood. This phenomenon is often accompanied by autoimmune salivary gland dysfunction, with serious consequences for oral health, and by numerous systemic disorders triggered, at least in part, by immune complex deposition. these symptoms characterize Sjogren's Syndrome, which affects more than one million American women over age 55. Recent subcellular fractionation and morphological studies indicate that Na,K-ATPase and other acinar cell plasma membrane proteins participate in an extensive recycling traffic to and from an intracellular pool, which appears to be organized into early and late endocytic compartments. Segregation mechanism appear to permit fluid phase traffic between the two compartments but allow Na,K-ATPase to travel from the late to the early compartment only in response to cholinergic stimulation. Excessive stimulation appears to alter the microdomain organization of the late compartment and to impair its ability to participate in intracellular fluid phase traffic. The existence of such an extensive, secretagogue- controlled intracellular traffic suggests a working hypothesis in which acinar cells trigger local autoimmune reactions by functioning analogously to specialized antigen-presenting cells. Preliminary data confirm that acinar cells contain a potentially immunogenic protein (LG- Ag2) and that they can express several components of the machinery for antigen presentation, including cathepsin B, which might excise immunogenic peptide fragments, and Class II histocompatibility molecules, which might bind immunogenic fragments and display them to T cells. It is also possible that additional peptides occurring in the lacrimal interstitium can provide accessory signals for T cell activation. The specific aims of the proposed studies are to: 1) Delineate and survey the microdomain organizations of the early and late endocytic compartments. 2) Identify mechanisms responsible for re-organizing the late endocytic compartment following optimal and excessive cholinergic stimulation. 3) Map the subcellular distributions of cathepsins B and D, LG-Ag2, and Class II histocompatibility molecules to determine whether they can accumulate in compartments that communicate with the plasma membrane. If the hypotheses explored by the project are proven correct, then progress will have been made in the understanding of events underlying insertion and retrieval of membrane transporters, and the stage will be set for attempts to understand T cell activation by acinar cells.