THE SURFACE OF RAT HEPATOCYTES CAN TRANSFER IRON FROM STABLE CHELATESTO EXTERNAL ACCEPTORS

The chelator diethylenetriaminepentaacetate (DTPA) forms a stable comp lex with iron that does not donate iron to transferrin under physiolog ical conditions, i.e., pH above 7 and isotonic milieu, It does, howeve r, deliver iron to hepatocytes, This uptake is initiated by a mobiliza tion of the metal from the complex by the cell surface. When an extern al chelator is added simultaneously, it can bind the iron and inhibit its accumulation by the cells. This is shown here with the impermeant siderophore conjugate hydroxyethyl-starch coupled desferrioxamine, as well as with apotransferrin, We also demonstrate exchange of iron betw een DTPA and holo-transferrin, or at least movement from the chelator to the protein, which may have lost its iron to the cell in advance, p roviding new binding sites for mobilized iron. The efficient hepatocyt e iron donor lactoferrin greatly stimulates iron uptake from DTPA, app arently by binding iron and transferring it into the cells by endocyto sis. Ferritin is unable to do this; therefore, the mobilization of iro n is not caused by a reducing activity at the cell surface, because ir on is readily transferred from DTPA to ferritin by the reductant ascor bic acid, The transfer process is dependent on the temperature, the ti me, and the amount of cells present, and is partly inhibited by sulfhy dryl reagents, We conclude that this activity represents a hitherto un identified first step in the movement of iron through the cell membran e and may be relevant for transferrin-bound, as well as for non-transf errin-bound, iron uptake by hepatocytes.