Cited by 117Iron Metabolism and DisordersCellular transport and secretionInfant Nutrition and Health

The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.

Cellular internalization of lactoferrin in intestinal epithelial cells

Ashida, Kinya, Sasaki, Hajime, Suzuki, Yasushi A., Lönnerdal, Bo·2004·BioMetals

Abstract

We studied the cellular internalization of lactoferrin (Lf) in an intestinal epithelial cell line, Caco-2, to investigate the mechanism of biological actions of ingested Lf. RT-PCR and Western blotting analyses revealed that differentiated Caco-2 cells express LfR mRNA and its protein with a 34 kD molecular weight under reducing conditions. Biotin-labeled Lf showed specific binding to the cellular membrane of differentiated Caco-2 cells with a dissociation constant (Kd) of 0.16 microM. The cellular internalization of Lf was studied in differentiated Caco-2 cells grown as monolayers on Transwell inserts, and compared to that of human transferrin (Tf). After labeling with fluorescent dye, either Lf or Tf was added to Caco-2 cells from the apical side or the basolateral one. Laser scanning confocal microscopy showed that labeled Lf was internalized only from the apical side and localized to the nuclei. On the other hand, labeled Tf was internalized from the basolateral side, not from the apical side, and localized in the cytoplasm. The internalization of labeled Lf was inhibited by excess of unlabeled Lf, but not of Tf. The internalization of labeled Lf, but not of labeled Tf, was also suppressed by heparin. This indicates that a heparin-binding site in the N-terminal region of Lf could be important for the internalization of Lf. These findings suggest that ingested Lf might be internalized by the intestinal epithelium in a manner different from Tf and might function in the nucleus.

Overview

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Registry

Crossref · 10.1023/b:biom.0000027710.13543.3f

Cites

17 of 17 references verified0 citation errors · 0 not checkable

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  • Lactoferrin can enter epithelial cells by receptor-mediated endocytosis and translocate into the nucleus to modulate pro-inflammatory gene expression in the host cell.

    “LF can enter epithelial cells by receptor-mediated endocytosis and translocate into the nucleus to modulate pro inflammatory gene expression in the host cell”

    From Iron in immune cell function and host defense (2021) · cites this paper as [84]

Citations

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Research works printed but not linked: 2

  1. Kawakami H, Lönnerdal B. 1991 Isolation and function of a receptor for human lactoferrin in human fetal intestinal brushborder membranes. Am J Physiol 261, G841-G846.
  2. Sasaki H, Yamaguchi M, Nakamura Y, Takahashi T, Yajima T, Kuwata T. 2002 Lactoferrin binds to and is incorporated into cells when it suppresses the LPS-induced production of TNF by macrophages. Biochem Cell Biol 80, 143.

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Metadata

Authors
Ashida, K., Sasaki, H., Suzuki, Y. A., & Lönnerdal, B.
Affiliations
  • University of California, Davis (US)
  • Meiji (Japan) (JP)
Corresponding author
Lönnerdal, Bo
Venue
BioMetals
Published
2004-06
Volume
17
Issue
3
Pages
311-315
ISSN
  • 0966-0844 (ISSN-L)
  • 1572-8773
OpenAlex
W2031636247
Cited by
117
References
17
Citations by year
2025: 4 · 2024: 3 · 2023: 5 · 2022: 10 · 2021: 6 · 2020: 10 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 3 · 2014: 2 · 2013: 5 · 2012: 9
FWCI
4.18
Type
journal article
Language
en
Open access
closed
Locations
  • BioMetals (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
Keywords
lactoferrin, cellular internalization, intestinal epithelial cells, Caco-2 cells, lactoferrin receptor, heparin-binding site, nuclear localization, transferrin, heparin, membrane binding
MeSH terms
Animals, Cell Membrane, Endocytosis, Epithelial Cells, Heparin, Humans, Intestinal Mucosa, Lactoferrin, Receptors, Cell Surface, Transferrin, Caco-2 Cells

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