Endocytosis and trafficking of human lactoferrin in macrophage-like human THP-1 cells (1)

Biochem Cell Biol. 2012 Jun;90(3):449-55. doi: 10.1139/o11-090. Epub 2012 Mar 1.


Different cell types have been reported to internalize lactoferrin (Lf) by specific or nonspecific receptors. Our studies focused on the endocytic pathway of human Lf in macrophage-like THP-1 cells. Lactoferrin was found to be internalized by THP-1 cells differentiated with phorbol myristate acetate. Incubation of cells with chlorpromazine and dansylcadaverine, inhibitors of clathrin-dependent endocytosis, led to a 50% inhibition of Lf internalization compared with untreated cells. Bafilomycin A1 and NH(4)Cl treatment also resulted in 40%-60% inhibition, respectively, suggesting that the internalization of Lf may partly be mediated by acidic endosome-like organelles. Endocytic uptake of Lf was also cholesterol-dependent, as shown by methyl-β-cyclodextrin or nystatin treatment of the cells prior to internalization. Partial colocalization of Lf and EEA-1, a marker specific for early endosomes, could be observed. Colocalization of Lf with a specific endoplasmic reticulum marker was also detected. Our results suggest that Lf is internalized mainly by the clathrin-dependent pathway in THP-1 cells and targets the ER. The physiological consequences of this intracellular trafficking will be the subject of future investigations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonium Chloride / pharmacology
  • Cadaverine / analogs & derivatives
  • Cadaverine / pharmacology
  • Cell Line
  • Chlorpromazine / pharmacology
  • Cholesterol / physiology
  • Endocytosis* / drug effects
  • Endoplasmic Reticulum / metabolism
  • Endosomes / drug effects
  • Endosomes / metabolism
  • Humans
  • Lactoferrin / metabolism*
  • Macrolides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Microscopy, Fluorescence
  • Protein Transport / drug effects


  • Macrolides
  • Ammonium Chloride
  • bafilomycin A1
  • Cholesterol
  • Lactoferrin
  • monodansylcadaverine
  • Cadaverine
  • Chlorpromazine