Neutrophil elastase increases airway epithelial nonheme iron levels.

Published

Journal Article

Alpha-1-antitrypsin (A1AT) deficiency is characterized by increased neutrophil elastase (NE) activity and oxidative stress in the lung. We hypothesized that NE exposure generates reactive oxygen species by increasing lung non-heme iron. To test this hypothesis, we measured bronchoalveolar lavage (BAL) iron and ferritin levels, using inductively coupled plasma (ICP) optical emission spectroscopy and an ELISA respectively, in A1AT-deficient patients and healthy subjects. To confirm the role of NE in regulating lung iron homeostasis, we administered intratracheally NE or control buffer to rats and measured BAL and lung iron and ferritin. Our results demonstrated that A1AT-deficient patients and rats post-elastase exposure have elevated levels of iron and ferritin in the BAL. To investigate the mechanism of NE-induced increased iron levels, we exposed normal human airway epithelial cells to either NE or control vehicle in the presence or absence of ferritin, and quantified intracellular iron uptake using calcein fluorescence and ICP mass spectroscopy. We also tested whether NE degraded ferritin in vitro using ELISA and western analysis. We demonstrated in vitro that NE increased intracellular non-heme iron levels and degraded ferritin. Our results suggest that NE digests ferritin increasing the extracellular iron pool available for cellular uptake.

Full Text

Duke Authors

Cited Authors

  • Fischer, BM; Domowicz, DAL; Zheng, S; Carter, JL; McElvaney, NG; Taggart, C; Lehmann, JR; Voynow, JA; Ghio, AJ

Published Date

  • October 2009

Published In

Volume / Issue

  • 2 / 5

Start / End Page

  • 333 - 339

PubMed ID

  • 20411049

Pubmed Central ID

  • 20411049

Electronic International Standard Serial Number (EISSN)

  • 1752-8062

International Standard Serial Number (ISSN)

  • 1752-8054

Digital Object Identifier (DOI)

  • 10.1111/j.1752-8062.2009.00151.x

Language

  • eng