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 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.
Huang
Y T
YT
Department of Medicine, Duke University Medical Center, Durham 27710, North Carolina, USA. huang002@mc.duke.edu
Ghio
A J
AJ
Nozik-Grayck
E
E
Piantadosi
C A
CA
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000037:antagonists & inhibitors; D001639:Bicarbonates / Q000378:metabolism; D001761:Bleomycin; D005293:Ferritins / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011652:Pulmonary Circulation / Q000502:physiology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism
D001457:Anion Exchange Protein 1, Erythrocyte; D001639:Bicarbonates; D014168:Transferrin; D001761:Bleomycin; D005293:Ferritins; D007501:Iron; D007781:Lactoferrin; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid