Lactoferrin interferes with uptake of iron from transferrin and asialotransferrin by the rat liver

Hu, Wei-Li; Regoeczi, E.; Chindemi, Paul A.; Bolyos, Maria

doi:10.1152/ajpgi.1993.264.1.g112

Cited by 12 publications

(25 citation statements)

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“…Lactoferrin may be removed by receptor-mediated endocytosis into phagocytic cells such as macrophages, monocytes and other cells of the reticuloendothelial system (25)(26)(27)(28). An alternative way of lactoferrin removal is direct uptake by the liver, involving Kupffer cells, liver endothelial cells and hepatocytes (29).…”

Section: Lactoferrin Metabolismmentioning

confidence: 99%

Lactoferrin: A multifunctional glycoprotein

Vorland¹

1999

APMIS

227

149

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Vorland LH. Lactoferrin: A multifunctional glycoprotein. APMIS 1999; 107:971-8 1.Lactoferrin is an iron-binding glycoprotein found in milk, exocrine secretions of mammals, and in secondary granules from polymorphonuclear neutrophils. This review describes the wide spectrum of functions ascribed to lactoferrin, with special emphasis on the antimicrobial properties of this protein, and its derived peptides.

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Section: Lactoferrin Metabolismmentioning

confidence: 99%

Lactoferrin: A multifunctional glycoprotein

Vorland¹

1999

APMIS

227

149

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“…Tf does not compete with Lf for binding and endocytosis of Lf protein by hepatocytes [8,9], although Lf can partially inhibit hepatocyte iron uptake from Tf presumably by competing with Tf for binding to cell-surface proteoglycans [26]. It is not known, however, whether iron associated with transferrin and Lf follow common or unique entry routes into hepatocytes.…”

Section: Modulation Of 59fe Uptake From Lfmentioning

confidence: 99%

Isolated rat hepatocytes acquire iron from lactoferrin by endocytosis

McAbee

1995

Biochemical Journal

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The iron-binding protein lactoferrin (Lf) present in blood is metabolized by the liver. Isolated rat hepatocytes vigorously endocytose bovine Lf via recycling Ca2(+)-dependent binding sites, but the uptake of iron from Lf by hepatocytes has not been examined. In this study, isolated rat hepatocytes were incubated with radiolabelled bovine Lf (125I-Lf, 59Fe-Lf or 125I-59Fe-Lf) at 37 degrees C, then washed at 4 degrees C in the presence of dextran sulphate with either Ca2+ or EGTA to distinguish between total bound and internal radioactivity respectively. Cells internalized 125I-Lf protein and Lf-bound 59Fe at maximal endocytic rates of 1700 and 480 mol.cell-1.s-1 respectively. When Lf was normalized for 59Fe content, these endocytic rates were equivalent and reflected an uptake potential of at least 3400 mol of iron.cell-1.s-1. Cells prebound with 125I-59Fe-Lf to Ca2+(-)dependent sites at 4 degrees C internalized more than 80% of both 125I-Lf protein and Lf-bound 59Fe approx. 6 min after warming to 37 degrees C at similar rates (125I-Lf: k(in) = 0.276 min-1, 59Fe: k(in) = 0.303 min-1). Within 4 h at 37 degrees C, cells had released 25% or less internalized Lf protein in the form of acid-soluble 125I-by-products but retained all the Lf-delivered 59Fe. Hyperosmotic disruption of clathrin-dependent endocytosis blocked the uptake of 125I-Lf and Lf-bound 59Fe. Incubation of cells with 125I-59Fe-Lf and a 100 molar excess of diferric transferrin reduced slightly the endocytosis of 125I-Lf protein and 59Fe accumulation. Treatment of cells with the ferric chelator desferrioxamine did not alter uptake of 125I-Lf protein or Lf-bound 59Fe, but the ferrous chelator bathophenanthroline disulphonate slightly elevated endocytosis of 125I-Lf protein and Lf-bound 59Fe. These findings indicate that Lf does not release its bound iron before endocytosis. It was concluded from this study that hepatocytes take up iron from Lf at high rates by a process that requires endocytosis of Lf-iron complexes.

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“…Alternatively, dissociation could be brought about by the alkalinity of bile (pH 8.0 to 8.1 in our rats) (i.e., close to the isoelectric point of lactoferrin), for the interaction of HSPG with transferrin, lactoferrin and lactoperoxidase is markedly pH dependent. It is strong at pH 5.6 but weakens as the pH increases to 7.4 (17).…”

Section: Discussionmentioning

confidence: 94%

“…This common component cannot be the regular transferrin receptor, for the receptor does not interact with lactoferrin (36). However, hepatic heparan sulfate proteoglycan (HSPG) does bind all the proteins under consideration here (17,37); therefore it could be the key membrane component initiating this particular form of transcytosis. Differences in fractional biliary transfer rates may therefore be an expression of unequal affinities for HSPG alone or, perhaps, for some other, not-yetidentified plasma membrane component(s).…”

Section: Discussionmentioning

confidence: 99%

“…We found earlier that lactoperoxidase, another protein with high affinity for the liver, inhibited 59Fe uptake by the liver from transferrin more efficiently than did a comparable dose of lactoferrin (17). The possibility thus arose that these three proteins bind competitively to the same plasma membrane component(s).…”

Section: Competitive Inhibition Of the Transfer Of Lactoferrin To Thementioning

confidence: 99%

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Transport of lactoferrin from blood to bile in the rat

Regoeczi

Chindemi

1994

Hepatology

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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.

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Lactoferrin interferes with uptake of iron from transferrin and asialotransferrin by the rat liver

Cited by 12 publications

References 0 publications

Lactoferrin: A multifunctional glycoprotein

Lactoferrin: A multifunctional glycoprotein

Isolated rat hepatocytes acquire iron from lactoferrin by endocytosis

Transport of lactoferrin from blood to bile in the rat

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