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

Oyebode Olakanmi; Stephen E McGowan; Michael B Hayek; Bradley E Britigan

doi:10.1172/JCI116310

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

Journal article

Open access

Peer reviewed

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

Oyebode Olakanmi, Stephen E McGowan, Michael B Hayek and Bradley E Britigan

The Journal of clinical investigation, Vol.91(3), pp.889-899

03/1993

DOI: 10.1172/JCI116310

PMID: 8383703

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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.

Bronchoalveolar Lavage Fluid

Isoenzymes - blood

Tetradecanoylphorbol Acetate - pharmacology

Catalase - blood

Humans

Superoxide Dismutase - blood

Reference Values

Iron Chelating Agents - metabolism

Nitrilotriacetic Acid - analogs & derivatives

Zymosan - pharmacology

Hydroxides - metabolism

Extracellular Space - metabolism

Ferritins - metabolism

Free Radicals - metabolism

Cell Membrane - metabolism

Macrophages - ultrastructure

Electron Spin Resonance Spectroscopy

Ferric Compounds - metabolism

Microscopy, Electron

Iron - metabolism

Hydroxyl Radical

Nitrilotriacetic Acid - metabolism

Smoking - metabolism

Macrophages - metabolism

Macrophages, Alveolar - drug effects

Macrophages, Alveolar - metabolism

Details

Title: Subtitle: Iron sequestration by macrophages decreases the potential for extracellular hydroxyl radical formation
Creators: Oyebode Olakanmi - Department of Internal Medicine, VA Medical Center, Iowa City, IA
Stephen E McGowan
Michael B Hayek
Bradley E Britigan
Resource Type: Journal article
Publication Details: The Journal of clinical investigation, Vol.91(3), pp.889-899
Publisher: United States
DOI: 10.1172/JCI116310
PMID: 8383703
ISSN: 0021-9738
eISSN: 1558-8238
Grant note: HL 39328 / NHLBI NIH HHS HL 44275 / NHLBI NIH HHS AI 28412 / NIAID NIH HHS
Language: English
Date published: 03/1993
Academic Unit: International Programs; Internal Medicine
Record Identifier: 9983984523502771

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