In this study we determined that dietary zinc supplementation improved lung bacterial clearance in alcohol-fed rats. Although there are many potential explanations for these salutary effects, it is intriguing that dietary zinc appeared to restore signaling through two important pathways in the alveolar macrophage that protect the lung against infection and oxidative stress. Specifically, it improved nuclear binding of PU.1, the master transcription factor for GM-CSF signaling that is crucial for alveolar macrophage maturation, differentiation, and immune functions including bacterial phagocytosis. In parallel, zinc supplementation restored nuclear binding of Nrf2, the transcription factor required to activate the antioxidant response element (ARE) and therefore critically involved in antioxidant defenses. Concomitant with increasing Nrf2 nuclear binding, zinc supplementation reversed the alcohol-induced oxidative stress, as reflected by restoring balance in the cysteine and cystine redox pair within the alveolar space. Taken together, these findings add to our previous study (Joshi et al., 2008) and further implicate zinc deficiency in the oxidative stress and immune dysfunction seen in the alcoholic lung. Translation of these experimental findings to the clinical setting could offer a potentially
