Transition from Normal to Hypersecretory Bronchial Mucus in a Canine Model of Bronchitis: Changes in Yield and Composition

Abstract

Density-gradient analysis was used to follow the transition from normal to hypersecretory bronchial mucus in a model of bronchitis induced in dogs by chronic exposure to SO2 gas. Aspirates of saline bronchial lavage were obtained by fiberoptic bronchoscopy from dogs before, during a 6- to 9-month exposure period to SO2 gas, and during a recovery period of similar duration. Prior to SO2 exposure, aspirates from all animals had a low yield of nondialyzable macromolecules (15 +/- 6 mg/aspirate) and similar composition. Specifically, epithelial glycoprotein of typical buoyant density was not detected; rather a glycoconjugate of higher buoyant density with features of both proteoglycan and glycoprotein was identified. Neutral lipids were predominant with lesser amounts of phospholipids; no glycolipids were detected. During the SO2 exposure period, aspirates from five of the eight dogs contained components similar in buoyant density to human bronchitic glycoprotein. Glycoprotein isolated from the canine aspirates was similar to glycoprotein isolated from human chronic bronchitic sputum, having the same carbohydrate composition and range of oligosaccharide size. Further, during and after SO2 exposure some aspirates contained appreciable amounts of glycolipids. These data demonstrate substantial similarities in composition between normal human and canine mucus and in mucus isolated from dogs with chronic airway inflammation induced by repeated irritant exposure and from human patients with chronic bronchitis.

Mucin gene expression in rat airways following infection and irritation

“…RNA from the heart and airways of specific pathogen-free rats was negative (Figure 2, and D lanes, Fig 3). The airway negativity is consistent with studies showing the paucity of mucous cells and mucin glycoprotein in the airways of specific pathogen-free rats (Fig 1, control, [22], [23]) as well as in healthy dogs [24], [25] and humans [26].…”

Animal models of asthma and chronic bronchitis

“…Changes in the nature of the mucus produced by SO 2 ‐exposed rats are also evident from the observation that with increasing time of exposure, the mucus becomes increasingly resistant to sialidase [38]. Changes in the amount and composition of mucus are also observed with chronic SO 2 exposure in dogs [50, 51], and in these animals changes in composition correlate with changes in the rheological properties of the mucus [52].…”

Long-term canine exposure studies with ambient air pollutants

“…There is now sufficient evidence from long-term animal studies to conclude that exposure to high levels of sulphur dioxide results in bronchitic lesions [17][18][19][20][21], high levels of nitrogen dioxide produce emphysematous lesions, and ozone induces fibrotic lesions [22]. To better understand the pulmonary responses to these and other air pollutants, especially when present at lower, more ambient levels, a number of long-term studies have been conducted using dogs exposed in chambers .…”

“…In these cases, dogs inhaled this gas through cuffed tracheostomy tubes at a concentration of 200 parts per million (ppm) for up to 18 months [17][18][19], or at a concentration of 50 ppm for 11 months [20,21]. …”