Iron sequestration by macrophages decreases the potential for extracellular hydroxyl radical formation

O. Olakanmi, S. E. McGowan, M. B. Hayek, B. E. Britigan

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Alveolar macrophages (AM) from smokers contain a much higher quantity of intracellular iron than AM from nonsmokers. Since some forms of iron will catalyze the formation of hydroxyl radical (·OH) from superoxide and hydrogen peroxide, the ability of AM derived from smokers and nonsmokers to generate ·OH was assessed. No detectable ·OH was produced by AM from either source, suggesting that iron sequestration by AM may limit the potential for ·OH-mediated lung injury. Consistent with this hypothesis, the ability of bronchoalveolar lavage fluid (BAL) from smokers and nonsmokers to act as an ·OH catalyst decreased after exposure to AM. We found that, like AM, human monocyte-derived macrophages (MDM) have the ability to acquire large quantities of iron from small low molecular weight iron chelates as well as decrease the ability of BAL to act as a ·OH catalyst. When MDM or AM were exposed to the iron chelates or BAL they were then able to generate ·OH after phorbol myristate acetate stimulation. However, when acutely iron- loaded or BAL-exposed MDM were placed in culture, their ability to produce ·OH decreased with time to the level of non-iron-exposed controls. This process correlated with iron translocation from the plasma membrane to the cytosol as well as a 3-9-fold increase in cellular ferritin. No increase in antioxidant enzyme levels or induction of the heat shock response was observed. Iron sequestration by macrophages may protect nearby cells from exposure to potentially cytotoxic iron-catalyzed oxidants such as ·OH.

Original languageEnglish (US)
Pages (from-to)889-899
Number of pages11
JournalJournal of Clinical Investigation
Volume91
Issue number3
DOIs
StatePublished - Jan 1 1993

Fingerprint

Alveolar Macrophages
Hydroxyl Radical
Iron
Macrophages
Bronchoalveolar Lavage Fluid
Iron Chelating Agents
Heat-Shock Response
Lung Injury
Tetradecanoylphorbol Acetate
Ferritins
Oxidants
Superoxides
Cytosol
Hydrogen Peroxide
Antioxidants
Molecular Weight
Cell Membrane
Enzymes

Keywords

  • cigarette
  • ferritin
  • free radical
  • superoxide

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Iron sequestration by macrophages decreases the potential for extracellular hydroxyl radical formation. / Olakanmi, O.; McGowan, S. E.; Hayek, M. B.; Britigan, B. E.

In: Journal of Clinical Investigation, Vol. 91, No. 3, 01.01.1993, p. 889-899.

Research output: Contribution to journalArticle

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