recently began investigating the potential role of zinc deficiency in the experimental alcoholic lung. We determined that chronic alcohol ingestion alters the expression of key zinc transporters in the gut and lung epithelia, and decreases zinc levels in the alveolar space and within the alveolar macrophages (Joshi et al., 2008). Remarkably, treating alveolar macrophages from alcohol-fed rats with zinc in vitro improved PU.1 nuclear binding and restored bacterial phagocytic capacity within 4 hours. In this current study, we extended those initial observations to ask two new questions: first, does dietary zinc supplementation restore alveolar macrophage function in vivo, and thereby produce a biologically significant benefit such as improving lung bacterial clearance? In parallel, does dietary zinc supplementation improve the redox balance within the alveolar space by increasing signaling through the ARE and its transcription factor, Nrf2? If so, then dietary zinc supplementation could be a simple and novel treatment for the alcoholic lung phenotype in humans, as zinc deficiency could represent a previously unrecognized mechanism that mediates alcohol-induced oxidative stress and immune dysfunction within the alveolar space.
