MUCINS ON THE SURFACE OF CULTURED AIRWAY GOBLET CELLS

点击翻译按钮获取中文摘要

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.