Changes in permeability of dog tracheal epithelium in response to hydrostatic pressure

We tested the hypothesis that, in asthma, the airway epithelial damage and leakage of blood proteins into the lumen are the result of edema and raised submucosal hydrostatic pressure. Sheets of dog tracheal epithelium were mounted in Ussing chambers, and the effects of transepithelial hydrostatic pressure differences (ΔP) on conductance (G), [³H]mannitol flux (J(man)), and fluorescein isothiocyanate-albumin flux (J(alb)) were determined. ΔP values of 20 cmH₂O directed from the mucosal to submucosal side of the tissue (m→s) had no significant effects on G, J(man), J(alb), or tissue ultrastructure. ΔP(s→m) caused increases in conductance (G) with a maximal effect at ~20 cmH₂O. ΔP(s→m) of 20 cmH₂O significantly (P < 0.05) increased G (4.3 ± 0.6 to 10.6 ± 1.6 mS/cm²), J(s→m)/(man) (18 ± 5 to 411 ± 54 nmol·cm^-2·h^-1), J(s→m)/(alb) (0.3 ± 0.1 to 6.0 ± 2.0 μg·cm^-2·h^-1), and J(m→s)/(alb) (0.7 ± 0.3 to 1.8 ± 0.4 μg·cm^{- 2}·h^-1). J(m→s)/(man) was not affected. On removal of ΔP, G and J(s→m)/(man) returned to preexposure values, though J(s→m)/(alb) remained slightly elevated at 1.1 ± 0.3 μg·cm^-2·h^-1. Morphologically, ΔP(s→m) caused dilation of lateral intercellular spaces, disruption of tight junctions, and submucosal edema. The large increases in s→m fluxes of albumin and mannitol are consistent with bulk flow of fluid toward the lumen via the areas of epithelial damage.