Structure and function of the extracellular layer of airspaces and its configuration following deposition of solid and liquid particles

Abstract

The purpose of this dissertation is to examine the structure and function of the extrace11ular layer from large airways to alveoli. Surface tension (y) was directly measured at the air-liquid interface of tracheas from rats and guinea pigs with a droplet spreading technique. A non-aqueous fixation method was used to preserve the extracellular layer including the surface active film for examination by electron microscopy ('EM). The function of the extracellular layer including the surface film was also studied in terms of its effect on particle displacement. Finally, a mode1 of injury to the airspaces was used to study the changes in the configuration of the extracellular layer after exposure to an acid aerosol. The extracellular layer of the airspaces was shown by EM to be continuous with a predominantly multilayered osmiophilic film at its surface. In the large airways, y was 33.3 ± 0.70 (SE) mN/m and 32.3 ± 0.68 (SE) mN/m for the normal rat and guinea pig trachea respectively. Guinea pigs exposed for 4 hours to sulphuric acid aerosol(43.3 • 4.57 (SD) mg/m3) developed a several-fold increase in the thickness of the mucus layer, with exudation of protein-Iike material. The osmiophilic surfactant film became irregularly thickened and multilayered. Despite these morphological changes, y remained normal. The capacity of the surface film to displace particles into the subphase was not compromised. The wetting and displacement of particles of different sizes and shapes were also studied in vitro. Small spherical particles (<30 µm in diameter) were more easily submersed into the liquid phase than larger particles; this effect was attributed to surface and line tension forces. Alveolar surfactant was studied using a captive bubble surfactometer to characterize the minimum surface tension (y min) obtained upon compressing surfactant films. The y min measured for lavaged material from the lungs of acid exposed guinea pigs was 12.1 ± 8.48 (mean ± SD) mN/m, significantly higher than for control guinea pigs-2.0 ± 0.43 mN/m-or for acid exposed rats-1.29 ± 0.11 mN/m. Both protein inhibition and lipid peroxidation appear to be involved in this model of injury to the extracellular layer.