Transport of lactoferrin from blood to bile in the rat

Abstract

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 micrograms/100 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 59Fe bound to lactoferrin accompanied the protein carrier to the bile. We 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.

Lactoferrin, a Pleiotropic Protein in Health and Disease

“…Overall, these data suggest the potential role of Lf in different organs and especially in the central nervous system, which requests thorough elucidation. Finally, studies in animals have shown that Lf may be transported into the circulation from the intestinal lumen and then excreted into the bile, thereby suggesting an enterohepatic circulation of Lf (68,168). The potential role of Lf in the enterohepatic circulation is not fully understood but it may be useful for iron homeostasis or in the regulation of intestinal inflammation mechanisms.…”

Identification and Isolation of a 45-kDa Calcium-Dependent Lactoferrin Receptor from Rat Hepatocytes

“…The liver regulates Lf's steady-state concentration (∼20 nM) by clearing it from the blood (Bennett & Kokocinski, 1979;Imber & Pizzo, 1983), most of it accumulating in hepatocytes (DeBanne et al, 1985;Imber & Pizzo, 1983;Ziere et al, 1992). Clearance of plasma Lf constitutes an important hepatic homeostatic function and may represent a significant iron-scavenging pathway (Ismail & Brock, 1993;Regoeczi et al, 1994).…”

Biliary lactoferrin concentrations are increased in active inflammatory bowel disease: a factor in the pathogenesis of primary sclerosing cholangitis?

“…Lactoferrin is transferred from the plasma into the hepatocyte largely by an active transport mechanism [54][55][56], and is probably routed to the bile canaliculus by vesicular transport [55,57]. Although only a small proportion of lactoferrin that is transferred from the plasma escapes degradation within the liver [55,58], the present results may also be explained by the presence of an enterohepatic circulation of lactoferrin. If so, then biliary lactoferrin concentrations would also be expected to be high in other inflammatory conditions in which systemic lactoferrin concentrations are increased [59,60].…”