Figure 1

Role of heme oxygenase and carbon monoxide in lung diseases. Heme oxygenase (HO) generates biliverdin IXα, ferrous iron, and carbon monoxide (CO) from the oxidation of heme. Exhaled CO reflects active heme metabolism. Inflammation, oxidative stress, and apoptosis represent an axis of disease, against which both endogenous HO activity and exogenous CO exert protective effects. CO may inhibit both inflammation and apoptosis. The toxicological properties of CO imply increased pro-oxidant activity; however, the pro-oxidant/and antioxidant consequences of CO in the physiological range remain unclear. The bile pigments biliverdin IXα and bilirubin IXα have demonstrated antioxidant properties, though their prospective roles in modulation of inflammation and apoptosis are currently under investigation. Iron (Fe) released from HO activity returns to a transient chelatable pool, where it may potentially promote oxidative stress and apoptosis. Induction of ferritin synthesis and sequestration of the released iron into ferritin may represent one possible detoxification pathway that limits the potential of iron in pro-apoptotic and pro-oxidative processes.