Acquisition of iron bound to low molecular weight chelates by human monocyte-derived macrophages

Oyebode Olakanmi, John B. Stokes, Bradley E Britigan

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The iron content of tissue macrophages increases under conditions of elevated extracellular iron. Studies of macrophage iron acquisition have generally focused on iron uptake from transferrin via receptor-mediated endocytosis. However, in vivo macrophages are also exposed to extracellular low m.w. iron chelates, particularly under conditions of iron overload. Therefore, we examined the mechanism of iron acquisition from low m.w. chelates by human monocyte-derived macrophages. Iron acquisition was influenced by the nature of the iron chelate: Fe-ascorbate > Fe-citrate > Fe- nitrilotriacetate (NTA) = Fe-ADP > Fe-glycyl-L-histidyl-L-lysine > Fe- diethylenetriamine pentaacetic acid >> Fe-EDTA = Fe-deferoxamine. With the exception of Fe-EDTA and Fe-deferoxamine, iron acquisition was greater than that with diferric transferrin. As assessed by using iron acquisition from NTA as a model, the process is temperature dependent, but pH independent (pH 5 to 8), and is influenced by the medium in which the cells are suspended. Acquisition is not affected by NaF, 2-deoxy-D-glucose, NaCN, or monocyte- derived macrophage exposure to trypsin, pronase, phenylarsine oxide, dihydrocytochalasin B, filipin, nystatin, or digitonin. The rate of iron acquisition from NTA is induced by iron pre-exposure as well as aluminum. In contrast, NTA chelates of other transition metals (Cd, Cu, Ga, Mn, and Zn) inhibited iron uptake by 20 to 80%. Unlike results obtained with Ga-NTA, Ga(NO3)3 increased iron uptake from NTA. Data obtained with neutrophils, and undifferentiated U937 and HL-60 cells were similar, which suggests that myeloid cells share this pathway for iron acquisition. Iron acquisition via this mechanism may allow macrophages and other leukocytes to clear local states of iron overload in vivo.

Original languageEnglish (US)
Pages (from-to)2691-2703
Number of pages13
JournalJournal of Immunology
Volume153
Issue number6
StatePublished - Sep 15 1994

Fingerprint

Iron
Molecular Weight
Macrophages
Iron Chelating Agents
Deferoxamine
Iron Overload
Edetic Acid
Filipin
Nystatin
Digitonin
Pentetic Acid
Pronase
Transferrin Receptors
HL-60 Cells
Deoxyglucose
Myeloid Cells
Endocytosis
Aluminum
Citric Acid
Adenosine Diphosphate

ASJC Scopus subject areas

  • Immunology

Cite this

Acquisition of iron bound to low molecular weight chelates by human monocyte-derived macrophages. / Olakanmi, Oyebode; Stokes, John B.; Britigan, Bradley E.

In: Journal of Immunology, Vol. 153, No. 6, 15.09.1994, p. 2691-2703.

Research output: Contribution to journalArticle

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abstract = "The iron content of tissue macrophages increases under conditions of elevated extracellular iron. Studies of macrophage iron acquisition have generally focused on iron uptake from transferrin via receptor-mediated endocytosis. However, in vivo macrophages are also exposed to extracellular low m.w. iron chelates, particularly under conditions of iron overload. Therefore, we examined the mechanism of iron acquisition from low m.w. chelates by human monocyte-derived macrophages. Iron acquisition was influenced by the nature of the iron chelate: Fe-ascorbate > Fe-citrate > Fe- nitrilotriacetate (NTA) = Fe-ADP > Fe-glycyl-L-histidyl-L-lysine > Fe- diethylenetriamine pentaacetic acid >> Fe-EDTA = Fe-deferoxamine. With the exception of Fe-EDTA and Fe-deferoxamine, iron acquisition was greater than that with diferric transferrin. As assessed by using iron acquisition from NTA as a model, the process is temperature dependent, but pH independent (pH 5 to 8), and is influenced by the medium in which the cells are suspended. Acquisition is not affected by NaF, 2-deoxy-D-glucose, NaCN, or monocyte- derived macrophage exposure to trypsin, pronase, phenylarsine oxide, dihydrocytochalasin B, filipin, nystatin, or digitonin. The rate of iron acquisition from NTA is induced by iron pre-exposure as well as aluminum. In contrast, NTA chelates of other transition metals (Cd, Cu, Ga, Mn, and Zn) inhibited iron uptake by 20 to 80{\%}. Unlike results obtained with Ga-NTA, Ga(NO3)3 increased iron uptake from NTA. Data obtained with neutrophils, and undifferentiated U937 and HL-60 cells were similar, which suggests that myeloid cells share this pathway for iron acquisition. Iron acquisition via this mechanism may allow macrophages and other leukocytes to clear local states of iron overload in vivo.",
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