Huang Y T, Ghio A J, Nozik-Grayck E, Piantadosi C A
Department of Medicine, Duke University Medical Center, Durham 27710, North Carolina, USA.
Am J Physiol Lung Cell Mol Physiol. 2001 Mar;280(3):L474-81. doi: 10.1152/ajplung.2001.280.3.L474.
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 lungs with ischemia-reperfusion (I/R) ventilated with normoxic (21% O(2)) or hypoxic (95% N(2)) gas mixtures. Some were perfused with bicarbonate-free (HEPES) buffer or treated with the anion exchange inhibitor DIDS. The control lungs released approximately 0.25 microg/ml of NHFe or 20% of the total lung NHFe into 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 reperfusion. NHFe release was attenuated by approximately 50% in both control and ischemic lungs by hypoxia and by >90% in control lungs and approximately 60% in ischemic lungs by DIDS and HEPES. Reperfusion injury was not affected by DIDS or HEPES but was attenuated by hypoxia. These results indicate that biologically nonreactive nonheme iron is released rapidly by the lung into the vascular space via mechanisms that are linked to bicarbonate exchange. During prolonged ischemia, redox-active iron is also released into the vascular compartment by other mechanisms and may contribute to lung injury.
在本研究中，我们假设肺会主动将多余的铁释放到循环系统中以调节铁稳态。我们测量了对照孤立灌注兔肺以及用常氧（21% O₂）或低氧（95% N₂）气体混合物通气的缺血再灌注（I/R）肺的灌注液中的非血红素铁（NHFe）。部分肺用无碳酸氢盐（HEPES）缓冲液灌注或用阴离子交换抑制剂DIDS处理。对照肺向未与铁蛋白、转铁蛋白、乳铁蛋白或博来霉素反应性结合的血管空间释放约0.25微克/毫升的NHFe或肺总NHFe的20%。I/R肺在缺血期间释放相似量的NHFe，在再灌注期间释放一些可检测到的博来霉素反应性铁。低氧使对照肺和缺血肺中的NHFe释放减少约50%，DIDS和HEPES使对照肺中的NHFe释放减少>90%，使缺血肺中的NHFe释放减少约60%。再灌注损伤不受DIDS或HEPES影响，但低氧可使其减轻。这些结果表明，生物学上无反应性的非血红素铁通过与碳酸氢盐交换相关的机制由肺迅速释放到血管空间中。在长时间缺血期间，具有氧化还原活性的铁也通过其他机制释放到血管腔中，并可能导致肺损伤。
