Differential localization of transferrin receptors and lipocalin-2 in rat hepatic and extra-hepatic organs during acute phase response

The transferrin receptors (TfR1, TfR2) and lipocalin-2 (LCN-2) are mainly involved in iron transport. We previously reported increasing amounts of liver cytoplasmic and nuclear iron content during acute phase response (ARP). Aim of the present study is to investigate intracellular localization of transferrin receptors and lipocalin-2 in liver compared to extra-hepatic organs under physiological and acute phase conditions. Immunohistochemistry was performed on 5 µm thick sections of hepatic and extra-hepatic tissues. Liver, spleen and heart cytoplasmic and nuclear proteins were used for Western blot analysis. By means of immunohistology TfR1 was detected in membranes and cytoplasm of liver and spleen cells while TfR2 showed nuclear expression mostly. In heart TfR1 and TfR2 both showed nuclear expression along with membranous and cytoplasmic localization, colocalization of TfR1 and TfR2 was also observed in spleen and heart. LCN-2 immuno-reactivity was detected in neutrophils and hepatocytes both. However, LCN-2 was detected in macrophages mostly, in spleen. Colocalization of LCN-2 with both transferrin receptors (TfR1, TfR2) was detected in hepatic and extra-hepatic tissues. The data presented demonstrate the differential and colocalization of transferrin receptors and LCN-2 in liver, spleen and heart. Western blot analysis of cytoplasmic and nuclear proteins from hepatic and extra-hepatic organs confirmed the immunihistology findings. Differential localization of iron transport proteins in different organs suggest their diverse role in these organs under physiological and pathological conditions. Colocalization of LCN2 with transferrin receptors clearly demonstrates its role in iron transport during acute phase conditions and presence of TfR1, TfR2 in cell nuclei demonstrate transport of iron to the cell nuclei needed for the integrity of life i.e. DNA repair, DNA replication and RNA metabolism.