Enhancement of the viscosity of mucin by serum albumin

Abstract

The interaction of serum albumin with a model epithelial mucin from pig stomach was explored by rotary viscometry. During 30 min of incubation of human serum albumin(20mg/ml) and pig gastric mucin (8mg/ml) in iso-osmotic buffers at 37 degrees C, the solution became markedly viscous. Viscosity enhancement was proportional to albumin concentration (2-40mg/ml), was most pronounced under conditions of low shear rate (less than 45S-1), and was considerably greater than the additive or multiplicative viscosity values calculated from albumin or mucin solutions measured separately. The viscous mucin-albumin complex was destroyed by high shear rates (greater than 90S-1), but slowly re-formed under zero shear conditions. Elevation of pH (7 to 9), ionic strength (0.1 to 1.0), and addition of disodium EDTA (5mM) did not cause marked or specific alterations in the viscosity of the mixture, suggesting that electrostatic interactions probably do not stabilize mucin-albumin complexes. Urea (7M) and heating (35 to 55 degrees C) caused a major increase in the viscosity of mucin and mucin-albumin mixtures, suggesting that rupture of hydrogen bonds, unfolding and partial denaturation of mucin promotes greater intertangling (possibly hydrophobic interactions) between mucin and albumin molecules. The implications of mucin-albumin interaction in diseases associated with mucus obstruction are briefly discussed.

Ex VivoSputum Analysis Reveals Impairment of Protease-dependent Mucus Degradation by Plasma Proteins in Acute Asthma

“…To investigate this possibility, we added human serum albumin (the most abundant protein in plasma [25]) to healthy sputum and measured elastic and viscous moduli over 24 hours. Albumin increased the elastic and viscous moduli immediately after addition to sputum (data not shown), a finding noted previously by others (26,27). However, albumin also prevented the usual declines in mucin cross-linking and length measured over 24 hours at 378C ( Figure 4D).…”

“…We hypothesized that protease-driven digestion of mucus is inhibited by plasma proteins, which are at increased concentrations in airway mucus during acute asthma exacerbation (6,31). Albumin comprises at least 60% of plasma proteins (26), and albumin concentrations are higher than normal in airway secretions in acute asthma (25). We found that albumin mixed with mucus inhibits its normal degradation and that albumin is a substrate of neutrophil elastase.…”

Pegylated GL67 lipoplexes retain their gene transfection activity after exposure to components of CF mucus

“…However, binding of albumin to mucin via hydrophobic interactions has been reported. 25 This may lower the concentration of 'free' albumin in the CF sputum, which can interact with the lipoplexes.…”

Rheological characterization of neutral and anionic polysaccharides with reduced mucociliary transport rates

“…A reconstituted porcine gastric mucus solution was prepared using a modification of the method reported by List et al 14 The use of lyophilized porcine gastric mucin was preferred in these studies because of the need for a matrix that contained limited nonglycoprotein contaminants that could contribute to the variability in the rheological properties of the final mucus gel. Lyophilized porcine gastric mucin Type II (40 mg/mL) was suspended in isotonic phosphate buffer (pH 6.6, the pH of mucus at the apical cell surface 15 ) containing 0.02% wt/vol sodium azide and stirred overnight at 4-C.…”