Iron overload and nitric oxide-derived oxidative stress following lung transplantation☆
Section snippets
Subjects and equipment
BALF samples from 21 subjects who had undergone LT at the Alfred Hospital between March 1991 and October 1994 were studied TABLE I, TABLE II. Among the study population, presence of BOS was defined as a “fixed” 20% or greater fall in forced expiratory volume in 1 second (FEV1) from the best achieved post-transplant in the absence of any other identifiable cause. Stable transplant recipients were defined as those who were clinically well, had well-preserved lung function (i.e., within 20% of
Hemosiderin score (HS) and BAL cell differentials
BAL cells from 19 of the 21 transplant subjects and 3 of the 11 controls examined stained positively for hemosiderin within macrophages (Figure 1 and Table III). HS was significantly higher in both ST (median 10.5, range 0 to 187) and BOS subjects (median 6.5, range 0 to 27) compared with normal controls (median 0, range 0 to 2; p = 0.001 and p = 0.01, respectively). The percentage of cells positive for hemosiderin was also significantly higher in ST (median 7.5%, range 0% to 74.5%) and BOS
Discussion
The current study demonstrates a significant increase in BALF ferritin concentration and HLM numbers in the lower respiratory tract of lung transplant recipients (LTRs). We believe these findings are very unlikely to just be the sequelae of previous biopsy procedures. In addition, we found elevated levels of nitrite in BALF of LTRs, suggesting the allograft may be subject to significant iron and NO-derived free-radical damage. Furthermore, we confirmed previous observations that BAL
References (42)
- et al.
Cytolytic therapy for the bronchiolitis obliterans syndrome complicating lung transplantation
Chest
(1996) Free radical chemistry of nitric oxide. Looking at the dark side
Chest
(1994)- et al.
Iron accumulation in lung allografts after transplantation
Chest
(1997) - et al.
Pro-oxidant iron is present in human pulmonary epithelial lining fluid; implications for oxidative stress in the lung
Biochem Biophys Res Commun
(1996) - et al.
Role for NF-κβ in the regulation of ferritin H by tumour necrosis factor
J Biol Chem
(1995) Ferritin as a source of iron for oxidative damage
Free Rad Biol Med
(1992)- et al.
Diagnostic value of haemosiderin laden macrophages in bronchoalveolar lavage
Chest
(1992) - et al.
Macrophage oxidation of L-arginine to nitric oxide, nitrite, and nitrate
J Biol Chem
(1989) - et al.
Nitric oxide mediates iron release from ferritin
Arch Biochem Biophys
(1990) - et al.
Metallothioein expression in human lung and its varying levels after lung transplantation
Chest
(1998)
Actuarial survival of heart-lung and bilateral sequential lung transplant recipients with obliterative bronchiolitis
J Heart Lung Transplant
Efficacy of transbronchial lung biopsy in the diagnosis of bronchiolitis obliterans in heart-lung transplant recipients
Transplantation
Architectural remodelling of lung allografts in acute and chronic rejection
Arch Pathol Lab Med
Bronchiolitis obliterans syndrome in lung transplant recipients is associated with increased neutrophil activity and decreased anti-oxidant status in the lung
Eur Resp J
Mechanisms of iron toxicity
Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with induction of nitric oxide synthaseeffect of inhaled glucocorticoid
FASEB J
Expression of nitric oxide synthase in lung transplant recipients with bronchiolitis obliterans
Eur Respir J
In stable lung transplant recipients, exhaled nitric oxide levels positively correlate with airway neutrophilia and bronchial epithelial iNOS
Am Rev Respir Crit Care Med
Nitric oxide generationa predictive parameter of acute allograft rejection
Transplantation
Iron-independent induction of ferritin H-chain by tumor necrosis factor
Proc Natl Acad Sci USA
Iron content in human alveolar macrophages
Eur
Cited by (25)
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).
Serum ferritin: Past, present and future
2010, Biochimica et Biophysica Acta - General SubjectsLung transplantation: does oxidative stress contribute to the development of bronchiolitis obliterans syndrome?
2009, Transplantation ReviewsCitation Excerpt :Chemically active iron, released from ferritin stores as a result of tissue damage, may possibly add to the oxidative burden after lung transplantation. A cross-sectional study, involving 14 stable lung recipients, 7 recipients with BOS, and 21 normal controls, was conducted by Reid et al [39] indicating that microvascular leakage within lung allografts contributes to OxS. Significantly elevated levels of ferritin (a storage form of iron, which can act as a prooxidant) and hemosiderin-laden macrophages in bronchoalveolar lavage fluid (BALF) were reported in both stable and BOS lung recipients when compared to controls (median, 49 μg/L [range, 1–950 μg/L] vs 2 μg/L [range, 0–16 μg/L]; P < .01).
Macrolides inhibit IL17-induced IL8 and 8-isoprostane release from human airway smooth muscle cells
2007, American Journal of TransplantationDisruption 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.
- ☆
Supported by NH & MRC, Australia.