Biochemical Properties of Tracheobronchial Mucins from Cystic Fibrosis and Non-Cystic Fibrosis Individuals

Abstract

ABSTRACT. Tracheobronchial mucins from healthy individuals and from patients with bronchial asthma or cystic fibrosis (CF) were isolated from lung mucus, purified, and their chemical and physical properties compared. Normal and asthmatic mucins required both a dissociating and a reducing agent for solubilization and exhibited identical chromatographic behavior on Sepharose 4B, Sepharose 2B, and hydroxylapatite and similar amino acid and carbohydrate compositions. In contrast, 1) C F lung mucins were solubilized in the absence of dissociating and/or reducing agents and 2) the majority of the C F mucins analyzed was eluted in the included volume of Sepharose 4B with K. , values of 0.3 + 0.1 rather than in the void volume and thus appeared smaller than normal and asthmatic mucins. The lower molecular weight mucins in C F sputum apparently are produced by bacterial or inflammatory cell proteinases since radiolabelled asthmatic mucin was digested to smaller fragments when incubated with crude C F lung mucosal samples. Furthermore, mucins secreted by tracheal explants from C F and from non-CF individuals eluted in the void volume on Sepharose 4B, suggesting that CF tracheobronchial mucins were not inherently smaller than non-CF mucins. (Pediatr Res 22: 545-551, 1987 mucus of exocrine glands or epithelial tubular systems of the respiratory, gastrointestinal, and reproductive tracts (2) which is the basis for the generally held assumption that C F mucus is "abnormal." Since mucus glycoproteins (mucins) are the macromolecules responsible for the viscoelastic properties of mucus (3-5), alterations in mucin structure could effect the physiological behavior of mucus.To date, the most comprehensive studies on C F mucins (6-8) have utilized TBM isolated from C F sputum as copious amounts of such material are readily available. There is limited information available on TBM from healthy airways primarily because of the difficulties in obtaining sufficient amounts of adequate material for analysis. Thus, insufficient information currently exists to determine whether C F and non-CF mucins are different (see Ref. 9 for review) although available studies suggest differences in sulfation of C F respiratory tract mucins (10). However, recent studies have suggested that TBM from healthy airways exhibit physical properties (size, chromatographic behavior on molecular sieving, solubility) different than those of mucins from pathological airways (I I-13). While isolating and purifying human mucins from normal and pathological mucus, we obtained results that indicated that C F TBM were considerably more heterogeneous and smaller in size than non-CF TBM. The smaller size of C F mucins in the samples analyzed could result from in vivo proteolysis, as C F airways are chronically infected with pathogens that produce proteinases (14, 15) and both C F sputum and bronchial washings contain high levels of extracellular proteinase activity (1 6-18). Alternatively, the smaller mucins could reflect inherent differences in C F mucins. These possibili...

Reassessment of the importance of mucins in determining sputum properties in cystic fibrosis

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Strategies for measuring airway mucus and mucins

“…Radiolabeling (metabolic labeling) of mucins also provides information regarding the total release of glycoproteins, as well as the functional state of the secreting cells [128, 129, 137, 140, 145, 146]. When radio-labeled monosaccharides (such as fucose) are used, they can also additional more specific information regarding glycosylation [129, 137].…”

Altered protease and antiprotease balance during a COPD exacerbation contributes to mucus obstruction

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