Chest
Iron Accumulation in Lung Allografts After Transplantation*
Section snippets
Subject Groups and Study Protocol
Five healthy volunteers (29 to 38 years old) were recruited to obtain control data for BAL measurements. The subjects were all nonsmokers and were not taking any medications. All had normal results of spirometry and chest radiographs.
Ten patients who underwent lung transplantation at Duke University were included in the study population (Table 1). All donor lungs received prostaglandin E in their main pulmonary artery, followed by 5 to 6 L infusion of modified Eurocollins solution for lung
Results
Microscopic examination of transbronchial lung biopsy tissue stained for iron, lactoferrin, and ferritin demonstrated evidence of iron sequestration in all of the cases. The Prussian blue stain showed the presence of iron primarily within alveolar macrophages (Fig 1, left panel, top and bottom), and these corresponded to the macrophages with fine brown cytoplasmic staining observed on hematoxylin-eosinstained sections. A similar distribution was observed with immunohistochemical staining for
Discussion
The presence of chemically reactive iron in tissue can increase the formation of reactive oxygen species that have the potential to injure tissues. Consequently, living systems have designed efficient means of controlling iron transport and storage in complexes that minimize the risk of electron transport to molecular oxygen. Despite this, an excess of intracellular iron stored in ferritin may increase the potential to promote the formation of metal-catalyzed hydroxyl radical.10
Our study shows
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Cited by (34)
Diesel exhaust PM2.5 greatly deteriorates fibrosis process in pre-existing pulmonary fibrosis via ferroptosis
2023, Environment InternationalCitation Excerpt :In addition, iron deposition accompanied by ferroptosis and EMT in alveolar type II cells suggested to promote the development of pulmonary fibrosis (Cheng et al., 2021). Further, the iron levels in the lung tissue and alveolar lavage fluid are elevated during lung transplantation, which may lead to occurrence of oxidative damage in the allografts and subsequent initiation of fibrosis (Baz et al., 1997). The present study also showed that PM2.5 induced the ferroptosis of TGF-β1-treated lung epithelial cells mediated by HO-1, and this process may be associated with impaired mitochondrial function.
Role of iron in the pathogenesis of respiratory disease
2017, International Journal of Biochemistry and Cell BiologyCitation Excerpt :TRALI is induced by transfusion of blood products, which is known to elevate systemic iron levels in patients, resulting in oxidative stress and a number of pathological consequences (Collard, 2014; Dani et al., 2004; Gattermann and Rachmilewitz, 2011; Jenkins et al., 2007; Peters et al., 2015). Increased iron accumulation is also observed following lung transplantation, with higher levels of iron accumulation associated with increased risk of acute organ rejection (Baz et al., 1997; Reid et al., 2001; Sandmeier et al., 2005). Pulmonary alveolar proteinosis (PAP) is characterised by abnormal accumulation of protein-rich surfactant and inflammation, with unusual accumulation in the lung of alveolar macrophages containing intracellular surfactant-like material and is associated with impaired lung function (Rosen et al., 1958; Shimizu et al., 2011).
Disruption of iron homeostasis and lung disease
2009, Biochimica et Biophysica Acta - General SubjectsSingle-institution Study Evaluating the Utility of Surveillance Bronchoscopy After Lung Transplantation
2009, Journal of Heart and Lung TransplantationCitation Excerpt :These percentages may be accurate, as corroborated by Baz et al,28 who found that 31% of their procedures had clinical indications. Other programs with surveillance protocols reported higher percentages of clinical indications, ranging from 43% to 63%.24,25,28,29 In the present study, 38 of 89 (43%) procedures in the SB group had clinical indications, primarily by PFT criteria, with pulmonary mechanics in 3 patients not improving as expected soon after transplantation.
Disruption of iron homeostasis in the lungs of transplant patients
2005, Journal of Heart and Lung TransplantationIron accumulation in lung allografts is associated with acute rejection but not with adverse outcome
2005, ChestCitation Excerpt :Both suggestions, however, seem to be impractical. In the literature,12, 13 it is argued that elevated iron content in the lung allograft may cause metal-induced injury and fibrosis mediated by iron-generated oxidative stress. However, from our results we cannot confirm this apprehension.