Chemical modulation of alveolar epithelial permeability

The volume and composition of fluid on the surface of the alveoli can affect alveolar ventilation, gas diffusion, and macrophage function. The passive permeability and active processes of the alveolar epithelial lining play a role in regulating surface fluid and are a potential site of damage by airborne chemicals. Like other epithelial barriers, the alveolar lining is permeable to lipophilic substances but restricts the transmural flow of small ions and hydrophilic nonelectrolytes (equivalent pore radius ca. 0.5-1.5 nm). The mammalian fetal lung and alveolar sacs of the adult bullfrog secrete Cl- and K+ into the airspace. Secretion by the fetal lung ceases at birth. Many environmental agents increase the permeability of the capillary endothelium and/or respiratory epithelium and induce pulmonary edema. Studies with bullfrog alveolar sacs have demonstrated that selective effects may or may not be followed by general derangement of the epithelial barrier. Exposure of the luminal surface to HgCl2 (10(-6) to 10(-4) M) induces a selective increase in Cl- secretion that is followed by a fall in transport and a general increase in ion permeation. CdCl2 (10(-5) to 10(-3) M) depresses ciliomotion on cells on the trabecula of the alveolus but does not affect Cl- secretion or transepithelial conductance. HNO3, like other mineral acids, increases conductance and the radii or pores in the barrier, whereas NaNO3 selectively inhibits Cl- secretion. Amphotericin B(10(7) to 10(-5) MJ) induces K+ secretion into the lumen of both bullfrog and rat lung. We conclude that environmental agents induce changes in epithelial function that may compromise the lung's ability to regulate respiratory fluid without destroying the characteristic permeability of the epithelial lining.