Physiological implications of mammalian ferritin-binding proteins interacting with circulating ferritin and a new aspect of ferritin- and zinc-binding proteins.

Abstract

Serum ferritin levels are relatively low (<1µg/ml) and serum ferritin generally disappears rapidly from the circulation (t 1/2<10min). There are various mammalian ferritin-binding proteins (FBPs) in the blood. Ferritin is cleared by direct uptake by ferritin receptors and by indirect receptor-mediated uptake of FBP complexed with ferritin. Mammalian ferritin binds both heme and iron, and binding occurs through two mechanisms: direct binding with ferritin to H-kininogen and anti-ferritin autoantibody, and indirect heme-mediated binding of fibrinogen and apolipoprotein B to ferritin. Anti-ferritin autoantibody and fibrinogen are proposed to be common mammalian FBPs, as is α2-macroglobulin. FBP-ferritin binding may affect blood coagulation and influence iron metabolism, oxidative condition, angiogenesis, inflammatory condition and immune response. Aside from apolipoprotein B, FBPs bind zinc ion to form antioxidant and anti-inflammatory agents. The possible simultaneous uptake of zinc ion with FBP-ferritin complex is likely to attenuate iron- and/or heme-mediated oxidative damage and inflammatory response.