Donnan mechanism of mucin release and conditioning in goblet cells: the role of polyions

Abstract

Mucin, the principal polymeric species in the mucus matrix, is condensed inside secretory granules and undergoes massive swelling upon exocytosis. Mucin swelling is governed by a Donnan equilibrium. However, the effect of polyions such as soluble proteins on the swelling of mucin granules has not been investigated. The experiments reported here were designed to evaluate the effect of albumin on swelling kinetics of mucin granules exocytosed from respiratory goblet cells in culture. The kinetics of swelling was monitored by video-microscopy. The diffusivity of newly released mucins, in the presence of different concentrations of serum albumin, was evaluated using the expression: D = r2f/tau where tau is the characteristic time of the swelling, and rf is the final equilibrium radius of the swollen granule. Preliminary results indicate that serum albumin at concentrations of 10(-7) M, which are equivalent to those found in the bronchial mucus of asthmatic or cystic fibrosis patients, can produce up to a 90% decrease in the diffusivity of newly released mucins. Albumin is commonly present on the surface of the respiratory mucosa, and its concentration is increased in asthma and other bronchial inflammatory diseases. The evidence presented here shows that soluble proteins can strongly modulate the rate of swelling of newly released mucins, as predicted by Donnan equilibrium. Since swelling is a critical determinant of mucus rheology, the concentration of plasma proteins on the mucosa could play an important role in the regulation of the rheological properties of mucus. Also, the characteristically thick mucus found in chronic bronchial inflammatory diseases could be at least partially explained by the high levels of albumin found in the airways of these patients.