The bile contains small quantities of lactoferrin, the origin of which is uncertain. For this reason, we studied the liver's capability of transferring lactoferrin from the plasma to the bile by injecting a dose (10 to 20 pg/lOO gm) of labeled bovine lactoferrin intravenously and following its appearance in bile over 3 hr. Whether diferric or iron free, lactoferrin peaked in the bile 35 min after administration (i.e., the same time as bovine lactoperoxidase and diferric rat transferrin). However, only a small portion of the lactoferrin dose (approximately 1%) was recovered with the bile in 3 hr. On the basis of autoradiographic evidence, the excreted lactoferrin appeared intact. The biliary excretion profile of albumin, a protein thought to reach the canaliculus by paracellular diffusion, was notably devoid of a peak. This, together with competition observed between lactoferrin and lactoperoxidase on one hand and 2Fe-transferrin and lactoferrin on the other for transfer to bile, suggests that lactoferrin is routed through the hepatocyte in vesicles. The process is initiated by binding to a plasma membrane component to which lactoperoxidase and 2Fe-transferrin can also bind. Most 6sFe bound to lactoferrin accompanied the protein carrier to the bile. W e conclude that under normal circumstances (i.e., when concentration of lactoferrin in the plasma is very low), lactoferrin transferred from plasma by the liver is probably not the major source of this protein in bile. (HEPATOLOGY 1994;19:1478-1482.)
Ladoferrin is a protein structurally related to transferrin such that both molecules are capable of strongly binding two atoms of iron (1). Whereas transferrin functions in uiuo primarily as a "plain" iron carrier, several possible functions have been proposed for lactoferrin (2). One of these-namely, that lactoferrin may play a role in intestinal iron absorption (31, gained experimental support in recent years (4,5), in particular by the isolation of a 130-kD duodenal protein that specifically binds ladoferrin (6). Of significance in this