Characteristics of chylomicron remnant uptake into rat liver.

We have investigated uptake of 125I-labeled chylomicron remnants into livers of rats in the presence of lactoferrin. This glycoprotein possesses a cluster of four arginines at the N-terminus similar to the arginine rich binding sequence of apoprotein E (apoE) to the LDL-receptor. We found that this protein inhibits uptake of 125I-chylomicron remnant radioactivity by 50% when measured as accumulation of radioactivity into the intact organ, and even more pronounced, over 75%, when measured as uptake into an endosomal fraction prepared therefrom. Provided that the arginine rich sequence is responsible for the inhibition, a similarity in the characteristics of binding of apoE to the LDL (low density lipoprotein)- and chylomicron remnant-receptor is likely. Second, transferrin having sequence homologies with lactoferrin, but lacking the arginine cluster does not interfere with chylomicron remnant uptake. Third, lactoferrin does not inhibit the uptake of chylomicron remnants by the spleen, which is most likely mediated through scavenger cells by a mechanism different from the chylomicron remnant uptake system of the liver. We hypothesize from this that lactoferrin specifically interferes with the physiologically relevant chylomicron remnant uptake system of the liver. Investigation of the mechanism of this inhibition will provide information about the physical characteristics of the remnant receptor system.