The regulation of iron release from the perfused rat liver.

Factors affecting iron efflux from the isolated perfused rat liver were studied following the intravenous administration of transferrin-(59)Fe or transferrin-(55)Fe administered to the rat from 1.5 h to 3.5 d before perfusion of the liver. The liver was perfused with rat red cells suspended either in rat plasma or Eagle's Basal Medium (EBM). The mean rate of efflux into a plasma pool containing normal iron and transferrin concentrations was 0.9% of the initial hepatic radioactive iron pool per hour. In EBM the average rate of efflux was 0.1%/h and this could be increased to the rate observed with plasma by the addition of apotransferrin. The rate of iron release from the liver in the presence of apotransferrin or other chelators was inversely proportional to the time of prelabelling. Maximal release rates were observed in livers perfused within 5 h of administering transferrin-(59)Fe to the rat. The effect of apotransferrin on efflux into EBM was concentration dependent. However, the maximum release of liver iron by apotransferrin occurred at physiological apotransferrin concentrations and addition of apotransferrin to plasma produced no increase in the rate of iron efflux. The stimulation of iron release in EBM caused by apotransferrin could be reversed by reducing the unsaturated iron binding capacity of the perfusate, either by addition of iron or removal of apotransferrin. However, increasing the iron concentration in the perfusate by the addition of iron-saturated transferrin without any reduction in the unsaturated iron binding capacity additionally increased iron release into plasma and EBM. This presumably reflects the exchange of plasma transferrin-(56)Fe for liver (59)Fe. Hence iron release measured in these studies represent the sum of two processes-net release of (59)Fe induced by apotransferrin and iron exchange between plasma and liver iron pools. Apotransferrin and desferrioxamine were equally effective, per unit iron binding capacity, in mobilizing liver iron, and may compete for the same parenchymal iron pool. This suggests that mobilization of iron by apotransferrin may depend solely on its ability to chelate ferric iron and not on a more specific ferroxidase activity or interaction with membrane receptors.