Vascular release of nonheme iron in perfused rabbit lungs

In this study, we hypothesized that the lung actively releases excess iron into the circulation to regulate iron homeostasis. We measured nonheme iron (NHFe) in the perfusate of control isolated perfused rabbit lungs and lung s with ischemia-reperfusion (I/R) ventilated with normoxic (21% O-2) or hyp oxic (95% N-2) gas mixtures. Some were perfused with bicarbonate-free (HEPE S) buffer or treated with the anion exchange inhibitor DIDS. The control lu ngs released similar to0.25 mug/ml of NHFe or 20% of the total lung NHFe in to the vascular space that was not complexed with ferritin, transferrin, or lactoferrin or bleomycin reactive. The I/R lungs released a similar amount of NHFe during ischemia and some bleomycin-detectable iron during reperfus ion. NHFe release was attenuated by similar to 50% in both control and isch emic lungs by hypoxia and by >90% in control lungs and similar to 60% in is chemic lungs by DIDS and HEPES. Reperfusion injury was not affected by DIDS or HEPES but was attenuated by hypoxia. These results indicate that biolog ically nonreactive nonheme iron is released rapidly by the lung into the va scular space via mechanisms that are linked to bicarbonate exchange. During prolonged ischemia, redox-active iron is also released into the vascular c ompartment by other mechanisms and may contribute to lung injury.