Aiway Mucins: experimental models for studies of secretions

Abstract: Mucins are essential components of the mucosal barrier. The complexity of the airway mucosal barrier is reflected in the lack of specific treatments to block mucin hypersecretion associated with several respiratory diseases such as chronic bronchitis, asthma and cystic fibrosis. Currently, researchers in the mucin field are confronted with a growing number of mucin genes. In order to understand the function and the role of individual members of the mucin family in health and disease adequate experimental models are needed. Using sputum as a model to study mucins secreted into the airways in cystic fibrosis, MUC5AC and MUC5B mucins were identified as the predominant gel-forming species. No major differences were found in the macromolecular properties of the MUC5AC and MUC5B mucins when compared with normal airway secretions. MUC2 was found in small amounts within the ‘insoluble’ extraction residue from the gel. Bovine trachea was established as an in vitro model. A ‘novel’ mucin-like highly radiolabelled component was identified both in organ cultures and primary cell cultures whereas the major mucins identified using chemical methods were not labelled. In the light of this finding, many studies where radiolabelling and the release of radiolabelled molecules have been used as a marker for large oligomeric gel-forming mucins, require re-interpretation. The suitability of mucin-secreting methotrexate-treated HT29 cell line and two subclones thereof as a potential alternative to animal models was investigated. Two major airway mucins MUC5AC and MUC5B were produced as well as some MUC2.