PSEUDOMONAS AERUGINOSA ADHESION TO MUC1 MUCIN

衬在气道腔表面的粘液作为主要的 物理化学屏障通过其粘弹性性质。此属性 主要由气道粘液的质量和 粘液糖蛋白或粘蛋白的浓度，其由 下面的上皮细胞粘蛋白是高分子量的糖蛋白 其中约80%的分子量由碳水化合物贡献 其详细结构尚不清楚。最近， 一种叫做MUC 1的粘蛋白， 也存在人乳腺癌和胰腺癌细胞表面 在包括气道上皮的正常上皮组织中。 的作用 然而，气道中的这些细胞表面粘蛋白是未知的。使用 原代仓鼠气管表面上皮细胞培养系统 在生物化学方面， 和药理学的粘蛋白，我们打算了解的作用，这些 融合时的MUC 1基因及其推导的氨基酸序列显示 它由676种氨基酸组成，其中包含以下四种主要的氨基酸： 结构域：（1）N-末端信号肽，（2）具有 20个氨基酸的12个串联重复，（3）跨膜结构域，和（4） C-末端胞质尾。酪氨酸磷酸化的存在 胞质尾区的共有基序非常有趣， 提示在信号转导中潜在作用。由于分泌粘蛋白在 已知气道与细菌，特别是假单胞菌结合 铜绿假单胞菌（PA）是导致各种临床疾病的主要细菌菌株， 在囊性纤维化患者中发现的并发症中，我们有粘蛋白， 上皮细胞系的表面增加PA与这些细胞的粘附， 上皮细胞我们推测气道表面的MUC 1粘蛋白 上皮细胞充当PA的受体，PA粘附到这些上皮细胞上， MUC 1粘蛋白导致一些迄今为止未知的上皮反应，这些反应是 可能与PA诱导的气道炎症相关。在这一提议中， 我们将首先证实MUC 1粘蛋白是PA粘附位点的这一发现， 探讨PA与MUC 1粘蛋白粘附的分子基础。 成功完成这项研究将为研究 上皮细胞对细菌粘附的反应， 在一般的气道炎症和囊性纤维化中很重要， 特别的。

Mucus lining the airway luminal surface serves as a primary physicochemical barrier through its visco-elastic property. This property of airway mucus is determined mainly by both the quality and concentrations of mucous glycoproteins or mucins that are secreted by the underlying epithelial cells. Mucins are high molecular mass glycoproteins in which about 80% of the molecular weight is contributed by carbohydrates whose detailed structures are still unclear. Recently it has been shown that a type of mucins called MUC1 mucins which were first identified on the surface of human breast and pancreatic cancer cells are also present in normal epithelial tissues including airway epithelium. The role of these cell surface mucins in the airway, however, is not known. Using a primary hamster tracheal surface epithelial (HTSE) cell culture system which has been relatively well characterized in terms of the biochemistry and pharmacology of mucins, we intended to understand the role of these MUC1 gene at confluence, and its deduced amino acid sequence revealed that it consists of 676 amino acids which contain the following four major domains: (1) N-terminal signal peptide, (2) the extracellular domain with 12 tandem repeats of 20 amino acids, (3) the transmembrane domain, and (4) the C-terminal cytoplasmic tail. The presence of tyrosine-phosphorylation consensus motifs in the cytoplasmic tail is very interesting and seems to suggest a potential role in signal transduction. Since secreted mucins in the airway are known to bind to bacteria , especially Pseudomonas aeruginosa (PA), a major bacterial strain responsible for various clinical complications found in patients with cystic fibrosis, we have mucins on the surface of an epithelial cell line increased PA adhesion to these epithelial cells. We hypothesize that MUC1 mucins on the surface of airway epithelial cells serve as a receptor for PA, and adhesion of PA to these MUC1 mucins lead to some as yet unknown epithelial responses which are likely associated with PA-induced airway inflammation. In this proposal, we will first confirm this finding that MUC1 mucins are PA adhesion sites, and then investigate the molecular basis of PA adhesion to MUC1 mucins. Successful completion of this study will provide a basis to study the epithelial responses to bacterial adhesion which may be crucially important in airway inflammation in general, and cystic fibrosis in particular.