Ceruloplasmin, transferrin and apotransferrin facilitate iron release from human liver cells.

The rate of iron release from HepG2 liver cells was increased not only by extracellular apotransferrin, but also by diferric transferrin, in a non-additive, concentration-dependent manner and to a similar magnitude. This suggests that rapid equilibration between receptor-mediated uptake and the release process determines net iron retention by the liver. Release was also accelerated by ceruloplasmin; most importantly, the effect of this protein was greatest when iron release was occurring rapidly, stimulated by apotransferrin, or under conditions of limited oxygen. Thus iron release involves both apotransferrin and ferrotransferrin, with ceruloplasmin playing a role in tissues with limited oxygen supply, as in the liver in vivo.