Airway Mucins: “Aircraft Carriers” in the Apical Surface Fluid

Abstract

Airway mucins, the major component of airway mucus or apical surface fluid that covers the entire surface of the airways, have been shown to possess multi-factorial functions that are necessary for first line defense, the major function of airway mucus. In this mini-review, I will provide some evidence, both theoretical and experimental, that the multi-factorial functions of airway mucins are most likely due to various bioactive proteins that are tightly associated with mucins. Thus, the first line defense of airway mucus requires both the mucociliary clearance and the activity of various bioactive proteins tightly associated with mucins, which depend on the quality and quantity of airway mucins.Keywords: Airway mucins; Physicochemical; Mucociliary; Viscoelasticity; Hydrophobicity Structure of MucinsMucus in the airway, also called the apical surface liquid, forms the first line defensive layer against particles or chemicals entering the lung. Airway mucus is produced by goblet cells of the underlying epithelium and mucous cells of the sub mucosal gland. Its defensive role is thought to be attributable to both its physical location and the physicochemical property through mucociliary clearance. The latter, more specifically referred to as the viscoelastic property of mucus, is controlled mainly by mucins which are present in mucus. Mucins are heavily glycosylated (>60% of molecular weight) and also negatively charged due to sialyation and sulfation of the oligosaccharides. Thus, the polydispersity of mucins in size and charge depends on the structure of their oligosaccharides and makes these molecules unique in both physiology and pathology. Studies with cultured airway goblet cells indicated that excessive production and secretion of mucins are induced by inflammatory mediators [1] suggesting that mucus hypersecretion in patients is due to airway inflammation.Twenty two mucin genes have been cloned in human of which 17 have been identified in the lung [2]. Among these 17 mucin genes, 5 mucins showed relatively high expression in the lung, which are MUC1, MUC4, MUC5AC, MUC5B and MUC16 [3]. While MUC5AC and MUC5B are secreted mucins or also called gelforming mucins, MUC1, MUC4 and MUC16 are cell surface mucins or also called membrane-tethered mucins. The membranetethered mucins can be shed by proteases [4] and therefore, mucins in the apical surface liquid consist of mainly these two types of mucins, i.e. full length MUC5AC and MUC5B and MUC1, MUC4 and MUC16 with only extracellular domains [3].