Abstract
Concentrations of ferritin in alveolar cells and on the alveolar surface are increased
in patients with a variety of respiratory disorders. Ferritin synthesis by cells is
modulated by iron content but is also influenced by stimuli other than iron. In this
study we sought to determine whether in vitro exposure to hypoxia- or nitric oxide
(NO)–induced ferritin accumulation or release by human alveolar macrophages
(AMs) or a lung cancer–derived epithelial cell line (A549). Changes in cell
content of iron and ferritin (L- and H-types), as well as ferritin content of cell
supernatants, were determined after in vitro exposure to hypoxia (1% or 10% O2, 18 hours) or the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 0.01–1.0 mmol/L, 18 hours). Exposure to 1% O2 increased ferritin content in both cell types (>fourfold increase; P < .005) without changing iron content. Treatment with SNAP increased ferritin
content of A549 cells in a dose-dependent manner, whereas treatment of AMs decreased
cellular iron and ferritin content and increased supernate ferritin content. Pretreatment
of cells with N-acetylcysteine (500 μmol/L) reduced hypoxia-induced ferritin accumulation
in alveolar cells and completely inhibited NO-induced ferritin accumulation in A549
cells. These findings indicate that exposure to 1% O2can increase ferritin content in alveolar cells, whereas NO can increase ferritin
content (A549 cells) or decrease ferritin content (AMs).
Keywords:
AM (alveolar macrophage), FBS (fetal bovine serum), IRP (iron-regulatory protein), MTT (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide), NAC (N-acetylcysteine), NAP (N-acetylpenicillamine), NO (nitric oxide), SDS (sodium dodecyl sulfate), SEM (standard error of the mean), SNAP (S-nitroso-N-acetylpenicillamine), SnPP (tin protoporphyrin)To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
October 29,
2002
Received in revised form:
October 29,
2002
Received:
June 17,
2002
Footnotes
Supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs; and by the American Lung Association, Arizona affiliate.
Identification
Copyright
© 2003 Elsevier Science Inc. Published by Elsevier Inc. All rights reserved.
