Disruption of iron homeostasis in the lungs of transplant patients.
BACKGROUND: Oxidative stress has been proposed as a mechanism of injury underlying obliterative bronchiolitis. Catalytically reactive iron is a potential source of reactive oxygen species in transplanted tissue. Using samples acquired from surveillance bronchoalveolar lavage (BAL), we tested the postulate that there is a disruption of iron equilibrium in transplanted lung, which can worsen with time. METHODS: A control group of 5 healthy, non-smoking volunteers underwent BAL. Five bilateral lung transplant patients underwent surveillance BAL with transbronchial lung biopsies. The BAL fluid concentrations of protein, albumin, total iron, lactoferrin, ferritin, transferrin receptor and total iron binding capacity were measured. RESULTS: The mean ages in the control and transplant groups were 25.0 +/- 2.4 and 34.6 +/- 5.0 years, respectively. Patients were transplanted for cystic fibrosis (n = 3), primary ciliary dyskinesia (n = 1) and bronchiolitis obliterans (n = 1). Surveillance bronchoscopies were performed at 100.6 +/- 63.3, 175.0 +/- 87.7 and 259.2 +/- 82 days post-transplant. No significant differences were noted in BAL protein, albumin and total iron binding capacity (TIBC) levels between the 2 groups. The BAL iron, transferrin, transferrin receptor, lactoferrin and ferritin levels were significantly elevated in transplant patients relative to controls. With time after transplantation, there were increases in lavage iron, transferrin receptor, lactoferrin and ferritin concentrations. CONCLUSIONS: Abnormally high levels of iron and its homeostatic proteins were found in the lung allografts, and levels appeared to increase with time. This supports a disruption in the normal homeostasis of this metal after transplantation and a potential role for a catalyzed oxidative stress in bronchiolitis obliterans. The use of iron-depleting therapy is a possible means for preventing injury in the lung allograft.
Pugh, C; Hathwar, V; Richards, JH; Stonehuerner, J; Ghio, AJ
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