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Original Research: DIFFUSE ALVEOLAR HEMORRHAGE |

Lane-Hamilton Syndrome: Ferritin Protects Lung Macrophages Against Iron and Oxidation

H. Lennart Persson, MD, PhD; Linda K. Vainikka, MSc; Hanna B. Eriksson, MD; Urban Wennerström, MD
Author and Funding Information

From the Division of Experimental Pathology (Dr Persson and Ms Vainikka) and Division of Pulmonary Medicine (Drs Persson and Eriksson), Linköping University, Linköping; and the Division of Medicine (Dr Wennerström), Hospital of Västervik, Västervik, Sweden.

Correspondence to: H. Lennart Persson, MD, PhD, Divisions of Pulmonary Medicine and Experimental Pathology, Linköping University, SE-581 85 Linköping, Sweden; e-mail: Lennart.Persson@lio.se


Funding/Support: This work was supported by grants to Dr Persson from the county council of Östergötland (ALF), the Medical Research Council of Southeast Sweden (FORSS), the Swedish Medical Society and Linköping Medical Society, and the Research Funds of LiÖ (Östergötland, Sweden), Apotekare Hedberg, and Olle Engkvist.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;139(2):361-367. doi:10.1378/chest.10-0818
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Background:  Lysosomal disruption and consequent apoptosis have been implicated in lung diseases characterized by iron overload. Free reactive iron in lysosomes sensitizes cells to oxidative stress. Apoptosis is prevented by heavy-chain (H)-ferritin, which can incorporate lysosomal iron into ferritin molecules. Tumor necrosis factor (TNF)-α stimulates the synthesis of H-ferritin. Idiopathic pulmonary hemosiderosis presents with the accumulation of iron and the upregulation of ferritin synthesis. We therefore analyzed the lysosomal response to oxidants and the role of H-ferritin synthesis in lung macrophages (LMs) harvested from the first Swedish case, to our knowledge, of Lane-Hamilton syndrome.

Methods:  Iron-exposed murine macrophages were used as a reference. Both cell types were stimulated with TNF-α (or not), then iron was assessed cytochemically and by atomic absorption spectrophotometry. H-ferritin expression was analyzed by Western blot and reduced glutathione (GSH) by spectrofluorometry. Following exposure to hydrogen peroxide, lysosomal membrane integrity and DNA degradation were analyzed by flow cytometry, whereas morphologic signs of apoptosis and necrosis were assessed by light microscopy.

Results:  GSH levels were approximately equal in LMs and murine macrophages. Although LMs contained much more iron than murine macrophages, lysosomal iron was bound in a harmless unreactive state by ample amounts of ferritin and hemosiderin, its lysosomal degradation product. Therefore, lysosomes of LMs were more oxidant resistant, and these cells were more adept at surviving oxidative stress. In both cell types, TNF-α prevented oxidant-induced lysosomal damage and cell death by upregulating synthesis of H-ferritin and GSH.

Conclusions:  Iron-overloaded LMs are equipped with an efficient armor of antioxidative mechanisms of which H-ferritin and hemosiderin seem to be particularly important.

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