LAUSR

Excessive production of intracellular ROS during prolonged exposure to hyperoxia compromises the ability of alveolar macrophages to phagocytose invading pathogens, leaving ventilated patients susceptible to pulmonary infection. Induction of the nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) pathway has been shown to regulate intracellular levels of ROS. The present study investigates whether sulforaphane (SUL) and resveratrol (RES), Nrf-2 inducers, can ameliorate hyperoxia-compromised macrophage functions. RAW 264.7 cells, a murine macrophage-like cell line, and bone marrow-derived macrophages (BMDM) were exposed to 95% O2 for 24 h in the presence or absence of SUL or RES. SUL or RES treatment ameliorated the increase of intracellular levels of ROS as well as hyperoxia-induced compromised phagocytic function. Furthermore, both SUL and RES were found to activate Nrf-2 and increase levels of the endogenous antioxidant compound, HO-1. These data suggest that activation of the Nrf-2 pathway can improve innate immunity, providing a therapeutic approach to the treatment of VAP.