title: Iron overload and nitric oxide-derived oxidative stress following lung transplantation.
abstract: BACKGROUND
  Reactive oxygen species (ROS) may contribute to airway injury and the development of the bronchiolitis obliterans syndrome (BOS) following lung transplantation (LT). Chemically active iron released from ferritin stores and nitric oxide (NO)-derived radicals may add to the oxidative burden.
  
  
  METHODS
  We determined the concentrations of ferritin and the aqueous NO derivative nitrite (NO2(-)) within bronchoalveolar lavage fluid (BALF) of 14 stable LT recipients (ST) and 7 subjects with BOS and 21 normal controls. We also assessed the relationship between BALF ferritin and hemosiderin-laden macrophages (HLMs) using a hemosiderin score (HS) and determined BALF albumin concentration as a marker of microvascular leakage.
  
  
  RESULTS
  BALF ferritin concentrations and HSs were significantly elevated in LT recipients overall compared with normal controls (p < 0.05). BALF NO2(-) levels were elevated in BOS subjects and STs compared with normal controls (p = 0.002 and p = 0.09, respectively), but there was no difference between transplant groups. BALF albumin concentrations were elevated in BOS patients compared with normal controls (p = 0.02) and ST (p = 0.05), but there was no difference between STs and controls. There was a significant relationship between BALF ferritin concentration and HS in LT recipients overall (r(s) = 0.7, p < 0.001). In BOS subjects, but not ST, BALF ferritin was significantly related to BALF albumin (r(s) = 0.8, p = 0.05) and there was a weak relationship with NO2(-) concentration (r(s) = 0.6, p = 0.1). BALF NO2(-) was strongly related to BALF % neutrophils in BOS subjects (r(s) = 0.9, p < 0.01), but there was no such relationship in STs.
  
  
  CONCLUSIONS
  Our findings suggest that the allograft could be subject to significant iron-generated oxidative stress, which may be exacerbated by NO and neutrophil-derived ROS, particularly in BOS. Microvascular leakage may be a feature of established chronic rejection, which potentiates the iron overload and contributes to further airway damage and remodeling.
authors.affiliation: Department of Respiratory Medicine, Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Reid
authors.forename: G
authors.initials: G
authors.lastname: Snell
authors.forename: C
authors.initials: C
authors.lastname: Ward
authors.forename: R
authors.initials: R
authors.lastname: Krishnaswamy
authors.forename: R
authors.initials: R
authors.lastname: Ward
authors.forename: L
authors.initials: L
authors.lastname: Zheng
authors.forename: T
authors.initials: T
authors.lastname: Williams
authors.forename: H
authors.initials: H
authors.lastname: Walters
mesh_terms: D000328:Adult; D001989:Bronchiolitis Obliterans / Q000175:diagnosis / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D005293:Ferritins / Q000378:metabolism; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000502:physiology; D006485:Hemosiderin / Q000378:metabolism; D006801:Humans; D019190:Iron Overload / Q000175:diagnosis / Q000503:physiopathology*; D016040:Lung Transplantation / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D011183:Postoperative Complications / Q000175:diagnosis / Q000503:physiopathology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D005293:Ferritins; D006485:Hemosiderin