Mucins, Mucus, and Sputum

Normal airway mucus lines the epithelial surface and provides an important innate immune function by detoxifying noxious molecules and by trapping and removing pathogens and particulates from the airway via mucociliary clearance. The major macromolecular constituents of normal mucus, the mucin glycoproteins, are large, heavily glycosylated proteins with a defining feature of tandemly repeating sequences of amino acids rich in serine and threonine, the linkage sites for large carbohydrate structures. The mucins are composed of two major families: secreted mucins and membrane-associated mucins. Membrane-associated mucins have been reported to function as cell surface receptors for pathogens and to activate intracellular signaling pathways. The biochemical and cellular functions for secreted mucin glycoproteins have not been definitively assigned. In contrast to normal mucus, sputum production is the hallmark of chronic inflammatory airway diseases such as asthma, chronic bronchitis, and cystic fibrosis (CF). Sputum has altered macromolecular composition and biophysical properties which vary with disease, but unifying features are failure of mucociliary clearance, resulting in airway obstruction, and failure of innate immune properties. Mucin glycoprotein overproduction and hypersecretion are common features of chronic inflammatory airway disease, and this has been the underlying rationale to investigate the mechanisms of mucin gene regulation and mucin secretion. However, in some pathologic conditions such as CF, airway sputum contains little intact mucin and has increased content of several macromolecules including DNA, filamentous actin, lipids, and proteoglycans. This review will highlight the most recent insights on mucus biology in health and disease. Normal airway mucus lines the epithelial surface and provides an important innate immune function by detoxifying noxious molecules and by trapping and removing pathogens and particulates from the airway via mucociliary clearance. The major macromolecular constituents of normal mucus, the mucin glycoproteins, are large, heavily glycosylated proteins with a defining feature of tandemly repeating sequences of amino acids rich in serine and threonine, the linkage sites for large carbohydrate structures. The mucins are composed of two major families: secreted mucins and membrane-associated mucins. Membrane-associated mucins have been reported to function as cell surface receptors for pathogens and to activate intracellular signaling pathways. The biochemical and cellular functions for secreted mucin glycoproteins have not been definitively assigned. In contrast to normal mucus, sputum production is the hallmark of chronic inflammatory airway diseases such as asthma, chronic bronchitis, and cystic fibrosis (CF). Sputum has altered macromolecular composition and biophysical properties which vary with disease, but unifying features are failure of mucociliary clearance, resulting in airway obstruction, and failure of innate immune properties. Mucin glycoprotein overproduction and hypersecretion are common features of chronic inflammatory airway disease, and this has been the underlying rationale to investigate the mechanisms of mucin gene regulation and mucin secretion. However, in some pathologic conditions such as CF, airway sputum contains little intact mucin and has increased content of several macromolecules including DNA, filamentous actin, lipids, and proteoglycans. This review will highlight the most recent insights on mucus biology in health and disease.