The LDL receptor family

Recently we described the specific inhibitory action of lactoferrin on chylomicron remnant (CR) uptake into the intact rat liver. Injection of lactoferrin but not transferrin (7 mg/100 g animal weight) together with radiolabelled CR inhibits in vivo uptake into liver by 50%. No inhibition of uptake into spleen was observed1. We demonstrated, that inhibition of uptake is directly connected to endocytosis, since endosomes purified by zonal rotor sucrose gradient centrifugation lack CR-radioactivity almost completely, when prepared from livers of rats that have been injected lactoferrin prior to labelled CR. The radioactivity associated with the liver in the presence of lactoferrin is exclusively located in compartments with a higher density, presumably plasma membranes or associated with endothelial cells. CR do not interact with lactoferrin and are processed normally by lipoprotein lipase in the presence of lactoferrin. Inhibition therefore takes place at an early step of the endocytotic uptake mechanism of CR located on the liver cell plasma membrane. Endocytosis is not blocked totally, as lactoferrin is taken up into endosomes. In addition, in vivo as well as in tissue culture we observed inhibition of CR uptake only and no effect was seen on receptor mediated LDL uptake or uptake of asialoorosomucoid2.