A Role for Ferritin in Hematopoiesis and the Immune System

Abstract

Elevated serum ferritin levels have been reported in a number of pathological states. These observations indicate that cells of the immune system can participate in the prevention of potential tissue toxicity from iron accumulation, and iron and iron-binding protein have important effects on immune systems. Ferritin is generally regarded as an intracellular iron storage protein. However, small amounts of ferritin circulate in the serum of normal individuals, and the physiological role of serum ferritin remains obscure. Although the function of ferritin is inevitably linked to iron metabolism, a role for ferritin in hematopoiesis and the immune system has drawn attention for years. Ferritin has an inhibitory effect on the in vitro growth of human hematopoietic progenitor cells and on the proliferation of T lymphocytes in vitro. Recently we report that ferritin may directly suppress the differentiation of human B lymphocytes maturing into antibody producing cells in vitro. In the present review, we summarise this field of research.

Immunosuppressive effects of melanoma-derived heavy-chain ferritin are dependent on stimulation of IL-10 production

“…In contrast, L-ferritin had a small stimulatory effect on anti-CD3-stimulated lymphocytes. Heart ferritin, which is higher in H-ferritin, 21 increased the levels of suppression in a dosedependent manner, whereas liver ferritin, reported to be rich in L-ferritin, 21 did not suppress lymphocyte proliferation. As shown in Figure 8, pre-incubation of increasing concentrations of rLferritin with a constant concentration of H-ferritin (45 M) resulted in inhibition of the suppressive effects induced by H-ferritin.…”

“…Morikawa et al 21 suggested that the biological properties of ferritin might vary depending on the ratio of heavy and light chains. In view of this, H-and L-ferritin expression was examined in melanoma cells and other non-malignant cells by flow cytometry.…”

“…In contrast, heart, kidney and placental ferritins are highly acidic because they are composed of mostly heavy chains. 21 Interestingly, ferritin in cancer cells consists mainly of heavy chains. 22,23 Others have suggested that there is another species of ferritin in cancer cells called super-heavy chain or P43.…”

Detailed proteome mapping of newly emerged honeybee worker hemolymph and comparison with the red-eye pupal stage

“…We showed that the ferritin level at the time of emergence increased in hemolymph compared with pupal hemolymph. In vertebrates, elevated serum ferritin levels have been reported in a number of pathological states (Morikawa et al 1995), and ferritin acts as an immunosuppressor, signaling molecule and immune regulator (Recalcati et al 2008). In Drosophila , overexpression of both the HCH and LCH genes is required to confer protection against oxidative stress (Missirlis et al 2007).…”

Serum ferritin regulates blood vessel formation: A role beyond iron storage

“…Ferritin does not have an obvious leader sequence, and the mechanism of its release from cells is unclear. Serum ferritin is increased during inflammation, which suggests that it may play a role in modulating inflammatory effects (2,3). In a recent issue of PNAS, Coffman et al (4) provide compelling evidence that serum ferritin regulates vascular remodeling and angiogenesis, demonstrating a role for serum ferritin in cell proliferation.…”