Liver endothelium mediates the uptake of iron-transferrin complex by hepatocytes.
We have previously shown that in the liver, transferrin (TF) receptors are limited to endothelial cells, and hepatocytes and Kupffer cells do not have TF receptors. To study the transport of iron into hepatocytes, we fractionated liver cell suspensions into endothelium and hepatocyte fractions. At 4 degrees C liver (but not umbilical cord) endothelium bound Fe-TF with a saturable kinetics. At 37 degrees C, the endothelial uptake was followed by its gradual release. Transendothelial transport of TF was visually demonstrated by perfusion of liver using colloidal gold-labeled TF. The released Fe-TF acquired the potential for binding to fresh target hepatocytes and binding was not inhibited by excess cold TF but was inhibitable by asialofetuin, suggesting galactosyl receptors and not TF receptors as a recognition mechanism. Isoelectrofocusing of the supernate after preincubation for 90 min at 37 degrees C with endothelial cells, demonstrated the presence of a newly generated band which co-migrated with asialotransferrin. We conclude that Fe-TF is initially removed by liver endothelium where it is modified probably by desialation to expose the galactosyl residues of the glycoproteins. The modified molecule is subsequently released and recognized by hepatocytes through a TF receptor-independent mechanism which may involve galactosyl receptors of hepatocytes. The findings indicate a key role for endothelium in the transport of Fe-TF into the liver and may suggest a physiological function for galactosyl receptors on hepatocyte surface.
D000818:Animals; D001692:Biological Transport; D004727:Endothelium / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000502:physiology*; D008854:Microscopy, Electron; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011990:Receptors, Transferrin; D014168:Transferrin / Q000378:metabolism*
D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron