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>Airway mucin glycoproteins in inflammatory conditions: Emphasis on equine recurrent airway obstruction, and the roles of bacterial endotoxin and elastase.
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Airway mucin glycoproteins in inflammatory conditions: Emphasis on equine recurrent airway obstruction, and the roles of bacterial endotoxin and elastase.
Mucin glycoproteins are responsible for imparting viscoelastic and adhesive properties to mucus. Biochemical methods to characterize and quantify mucus in the airways of horses have not been described to date. Bacterial endotoxin, a component of Gram-negative bacterial cell walls and a powerful inflammagen, has been used in rodents to induce airway changes that include increased mucus production. Detailed information concerning secretion of specific mucin molecules from pulmonary airways of rats has not been reported, however.; The overall goals of this research project were to quantify mucus levels in the airways of animals with specific inflammatory conditions, and to better characterize the molecular composition for the mucous layer in these animals. Main hypotheses tested were (1) increased airway mucus is a persistent phenomenon in recurrent airway obstruction (RAO)-affected horses; (2) airway levels of the mucin-associated sialyl Lewis X (SLeX) tetrasaccharide increase during inflammatory conditions; and (3) rats developing airway inflammation following bacterial endotoxin exposure produce and release specific mucins into airway lumens in a distinct temporal pattern. To test these hypotheses, research presented in this thesis details biochemical quantification and characterization of specific mucin-associated structures in (a) control and RAO-affected horses, both stabled and at pasture; and (b) rats exposed to hay dust or endotoxin.; Increased airway mucus, as measured by level of α-1,2 fucose, a hexose sugar associated with mucin molecules produced by secretory mucous goblet cells, was detected in bronchoalveolar lavage fluid (BALF) of RAO-affected horses both during acute disease and in clinical remission. Persistent mucin increases in RAO horses indicated long-term airway epithelial changes in diseased horses, possibly related to prolonged inflammatory activity.; In rats, endotoxin and hay dust exposures resulted in increased amounts of stored and secreted mucosubstances as compared to saline controls. Levels of soluble mucins possessing the sialyl Lewis X tetrasaccharide structure, detected by immunohistochemistry to be cell surface-associated, were increased in rat BALF at 6 hours after exposure to endotoxin, whereas α-1,2 fucose-possessing glycoprotein levels in BALF did not increase until 24 hours post-exposure. These findings indicate that there is a temporal pattern to the composition of airway mucus that is produced following endotoxin exposure, with an early release of membrane-associated mucins into airway lumens, followed by release of secretory mucins from airway goblet cells.
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