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Ferro-mitogens: iron-containing compounds with lymphocyte-stimulatory properties
A Novogrodsky1, M Suthanthiran, K H Stenzel
1Rogosin Institute, Cornell University Medical Center, New York, New York.
Abstract:
Ferric ammonium citrate (FAC) is nonmitogenic for human peripheral blood mononuclear cells (PBM) but has a potent mitogenic activity in the presence of IL-2. FAC in the presence of IL-2 increases the number of human peripheral blood mononuclear cells (PBM) expressing receptors for IL-2 and transferrin. FAC also markedly stimulates human PBM treated with supraoptimal, nonmitogenic concentrations of Con A. FAC, in the presence of IL-2, is a T-cell mitogen with a stringent requirement for macrophages. FAC stimulates the production of TNF-alpha and IFN-gamma in human PBM, and this effect is potentiated by IL-2. Thiourea and 3-amino-1,2,4-triazole selectively inhibit mitogenesis induced by FAC, indicating that oxygen radicals or peroxidase may mediate the triggering signal induced by this mitogen. In addition to hemin, as we have previously reported, and FAC, a variety of iron-containing proteins have lymphocyte stimulatory properties in combination with IL-2. They include horseradish peroxidase, cytochrome c, myoglobin, and transferrin. We have given the name ferro-mitogens to this group of compounds.
Insights
Ferric ammonium citrate (FAC) acts as a T-cell mitogen with Interleukin-2 (IL-2), stimulating human peripheral blood mononuclear cells (PBM). This effect, potentiated by IL-2, involves iron-containing compounds and suggests a role for oxygen radicals.
Area of Science:
- Immunology
- Cell Biology
Background:
- Ferric ammonium citrate (FAC) is typically nonmitogenic for human peripheral blood mononuclear cells (PBM).
- Interleukin-2 (IL-2) is crucial for T-cell proliferation and function.
Purpose of the Study:
- To investigate the mitogenic potential of Ferric ammonium citrate (FAC) in combination with IL-2.
- To explore the role of macrophages and signaling pathways in FAC-induced PBM stimulation.
Main Methods:
- Culturing human peripheral blood mononuclear cells (PBM) with FAC and IL-2.
- Assessing cell proliferation and receptor expression (IL-2, transferrin).
- Investigating the effects of Concanavalin A (Con A) and inhibitors like thiourea and 3-amino-1,2,4-triazole.
Main Results:
- FAC with IL-2 significantly increases PBM proliferation and expression of IL-2 and transferrin receptors.
- FAC acts as a T-cell mitogen requiring macrophages and potentiates IL-2-induced TNF-alpha and IFN-gamma production.
- Inhibitors suggest oxygen radicals or peroxidase mediate FAC-induced mitogenesis.
Conclusions:
- Ferric ammonium citrate (FAC) is a potent ferro-mitogen for human PBM when combined with IL-2.
- The mitogenic activity involves macrophage-dependent T-cell activation and cytokine production.
- Oxygen radicals likely play a role in the signaling pathway of this ferro-mitogen class.