MUCINS ON THE SURFACE OF CULTURED AIRWAY GOBLET CELLS

气道腔表面衬里的粘液是主要的 宿主的物理化学屏障及其粘弹性的变化 属性会导致异常的粘液纤毛清除，从而导致各种 肺部疾病。粘液的粘弹性为 主要由分泌的粘液糖蛋白或粘蛋白贡献 由两种类型的呼吸道细胞组成：表面上皮的杯状细胞 以及粘膜下腺的粘液细胞。多年来，我经历了 我一直致力于调节杯状细胞粘蛋白的释放 特征良好的体外模型系统，原代仓鼠气管 表面上皮(HTSE)细胞培养系统。我最近发现 有一些粘蛋白样糖蛋白(MLGP)紧密地结合在 融合的HTSE细胞的顶面。根据初步数据， 假设一些杯状细胞粘蛋白是(I) 锚定在顶端细胞表面，和(Ii)由MUC1粘蛋白编码 基因(S)，以及(Iii)可能受G蛋白偶联调控 磷脂酶C和蛋白激酶C我建议检验这些假说 通过：(I)从质膜中鉴定和纯化MLGP和 进一步表征了化学结构和物化性质 这些MLGP的属性；(Ii)确定这些MLGP是否 由粘蛋白基因编码；以及(Iii)确定这些细胞 表面MLGP可由已被证明具有刺激作用的试剂释放 这些细胞释放粘蛋白。从这些方面得到的结果 考虑到这些实验将是至关重要的 数百万个道尔顿糖蛋白与极其复杂的 物化性质被固定在高脚杯的顶端表面 细胞，与腔内容物直接接触。因此，这些 细胞表面粘蛋白可能在细菌黏附中发挥关键作用， 不同管腔内容物对上皮细胞的损伤及肺部用药 分娩，尤其是对患有以下两种疾病的患者进行基因治疗 囊性纤维化或肺气肿。另一方面，我们对 这些细胞表面粘蛋白将帮助我们更好地理解 健康和疾病中的呼吸道杯状细胞。

Mucus lining the airway luminal surface serves as a primary physicochemical barrier for the host, and alterations of its viscoelastic property results in abnormal mucociliary clearance which leads to various pulmonary diseases. The viscoelastic property of the mucus is contributed mainly by mucous glycoproteins or mucins which are secreted by two types of airways cells; the goblet cells of the surface epithelium and the mucous cells of the submucosal gland. Over the years, I have been working on the regulation of the goblet cell mucin release using a well-characterized in vitro model system, a primary hamster tracheal surface epithelial (HTSE) cell culture system. I have recently found that there are some mucin-like glycoproteins (MLGP) tightly bound to the apical surface of confluent HTSE cells. Based on preliminary data, the hypotheses have been developed that some goblet cell mucins are (i) anchored on the apical cell surface, and (ii) encoded by MUC1 mucin gene(s), and (iii) possibly regulated by the G protein-coupled phospholipase C and protein kinase C. I propose to test these hypotheses by: (i) identifying and purifying MLGP from the plasma membrane and further characterizing the chemical structure and the physicochemical properties of these MLGP; (ii) determining whether or not these MLGP are encoded by MUCI mucin genes; and (iii) determining whether these cell surface MLGP can be released by agents which have been shown to provoke mucin release from these cells. The result obtained from these experiments will be crucially important considering that these multimillion dalton glycoproteins with the extremely complex physicochemical property are anchored to the apical surface of the goblet cells, which are in direct contact with the luminal content. Thus, these cell surface mucins may play crucial roles in bacterial adhesion, epithelial cell injuries to various luminal contents, and pulmonary drug delivery, especially for gene therapy for patients suffering from either cystic fibrosis or emphysema. On the other hand, our understanding of these cell surface mucins will help us better understand the role of airways goblet cells in health and disease.