Impact of zinc deficiency on the alveolar epithelial barrier function

Abstract

Normal alveolar function depends on the ability of the epithelial cells to form tight junctions. We have shown that chronic ethanol ingestion increased alveolar epithelial cell permeability, and rendered the lung susceptible to acute injury. Alcoholics are known to be zinc deficient, and zinc is implicated in diverse cellular function including membrane stability. Therefore, we hypothesized that zinc deficiency at the cellular level can lead to alveolar epithelial barrier dysfunction, and that it might be possible to rescue these cells from further damage with zinc supplementation. We treated alveolar epithelial cell lines with or without the zinc chelator TPEN (5μM) for 48 hr, then washed the cells and cultured them for 6 days with or without zinc acetate (10μM). Treatment with TPEN significantly increased the alveolar epithelial permeability, as reflected by the flux of radioactive sucrose, and zinc supplementation restored it to the control level. In parallel, in vitro zinc supplementation tightened the barrier in epithelial cells from chronic alcohol‐fed rats. In addition, zinc acetate (2 mg/liter) added to the diets of rats for 3 wks while recovering from 6 wks of alcohol ingestion rescued alveolar epithelial cells from alcohol‐induced barrier dysfunction. These data suggest that zinc deficiency may be one of the factors responsible for alcohol‐induced alveolar epithelial barrier dysfunction, and that it might be possible to improve the alveolar epithelial barrier in alcoholics with zinc supplementation.