Endothelial transcytosis of iron-transferrin in the liver does not involve endosomal traffic.
Through a process resembling receptor-mediated internalization, liver endothelium binds and internalizes iron-transferrin (Fe-Tf) complexes, transporting them from the luminal to abluminal side. Since in most systems, the path of receptor-mediated endocytosis leads to the endosomal compartment where the medium is acidified, it is expected that Fe and Tf become dissociated in this acidified medium. However, experiments with double labeling (59Fe, 125I-Tf) indicate that these remain associated. To determine whether the endosomal pathway is used in the course of transendothelial transport of Fe-Tf, experiments were done by incubating purified liver endothelium with radiolabeled Fe-Tf in the presence and absence of endosomal inhibitors, NH4Cl, ethylamine and monensin. The discharge of radiolabeled protein was measured as a function of time. While there was an early phase inhibition in the presence of endosomal inhibitors, the discharge of Tf by endothelium in the presence of inhibitors, reached a plateau comparable to control cells after 4 h, indicating that endosomal inhibition does not inhibit transendothelial transport of Tf and, thus, the transport does not involve endosomal traffic.
Omoto
E
E
University of Mississippi School of Medicine, Jackson.
Minguell
J J
JJ
Tavassoli
M
M
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004705:Endocytosis; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005021:Ethylamines / Q000494:pharmacology; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008985:Monensin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014168:Transferrin / Q000378:metabolism*
D005021:Ethylamines; D014168:Transferrin; D000643:Ammonium Chloride; D008985:Monensin; D007501:Iron; C041564:ethylamine