PSEUDOMONAS AERUGINOSA ADHESION TO MUC1 MUCIN

气道腔表面衬里的粘液是主要的 通过其粘弹性性质形成的物理化学屏障。此属性 主要由呼吸道粘液的性质和性质决定 分泌的粘液糖蛋白或粘蛋白的浓度 下面的上皮细胞。粘蛋白是一种高分子质量的糖蛋白 其中约80%的分子量由碳水化合物贡献 其详细结构仍不清楚。最近，它被展示出来了 一种叫做MUC1型粘蛋白的粘蛋白在 人乳腺癌细胞和胰腺癌细胞的表面也存在。 在包括呼吸道上皮在内的正常上皮组织中。的作用 然而，呼吸道中的这些细胞表面粘蛋白尚不清楚。使用 原代金黄地鼠气管表面上皮细胞培养体系 在生物化学方面已经得到了相对较好的表征 和粘蛋白的药理学，我们打算了解它们的作用 MUC1基因融合，并揭示了其推导的氨基酸序列 它由676个氨基酸组成，包含以下四种主要成分 结构域：(1)N-末端信号肽，(2)具有 20个氨基酸的12个串联重复序列，(3)跨膜区，和(4) C-末端胞质尾部。酪氨酸磷酸化的存在 细胞质尾部的共识图案非常有趣，似乎 暗示了它在信号转导中的潜在作用。自分泌粘蛋白以来 已知呼吸道与细菌结合，尤其是假单胞菌 铜绿假单胞菌(PA)是一种主要的临床致病菌 在囊性纤维化患者中发现并发症，我们用粘蛋白 上皮细胞系的表面增加了PA对这些细胞的黏附 上皮细胞。我们推测呼吸道表面的粘蛋白MUC1 上皮细胞是PA的受体，PA与这些细胞的黏附 MUC1粘蛋白导致一些未知的上皮反应，这些反应是 可能与PA诱导的呼吸道炎症有关。在这份提案中， 我们将首先确认这一发现，即MUC1粘蛋白是PA黏附位点， 进而探讨PA与MUC1粘蛋白黏附的分子基础。 这项研究的成功完成，将为研究 上皮细胞对细菌黏附的反应可能是至关重要的 在呼吸道炎症和囊性纤维化中起重要作用 很特别。

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.