Lactoferrin-lipopolysaccharide interactions. Effect on lactoferrin binding to monocyte/macrophage-differentiated HL-60 cells

K. Miyazawa, C. Mantel, L. Lu, D. C. Morrison, H. E. Broxmeyer

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82 Scopus citations


Lactoferrin (LF) has been implicated in a number of functions including the negative regulation of myelopoiesis in vitro and in vivo, an effect mediated by suppression of cytokine release from monocytes/ macrophages. This suppression is abrogated by bacterial LPS. In the present study, HL-60 cells were induced to differentiate to monocytes/macrophages by 12-O-tetradecanoyl phorbol-13-acetate, and LF-binding assays were performed. After differentiation, HL-60 cells showed a twofold increase of LF-binding sites with no difference in the specificity or affinity of LF between pre- and post-differentiated cells. CD11a, CD11b, and CD11c Ag, which have been associated with specific binding sites for LPS on monocytes/macrophages, were also increased three- to fourfold after differentiation. With the use of this system, the effect of LPS on LF binding was studied. At 37°C, LPS enhanced LF binding on HL-60 cells, especially after differentiation. Conversely, at 4°C, LPS inhibited LF binding. There was little effect of temperature on LF binding in the absence of LPS. In the presence of polymyxin B sulfate, the enhanced LF binding by LPS was abrogated. Also, pretreatment with mAbCD11 and/or mAb5D3, which are associated with or directed against candidate LPS receptors, reduced LF binding. Cross-linking studies using an iodinated, photoactivatable LPS derivative ([125I]ASD-LPS) demonstrated directly the specific binding of LPS to LF. These data indicate a dichotomous nature of LF binding on monocyte/macrophage-differentiated HL-60 cells - one being mediated by specific LF receptors whereas the other is apparently mainly via LPS receptors after formation of an LF-LPS complex. These interactions, for which a model is proposed, help to explain the mechanism behind LPS abrogation of the myelopoietic suppressive effects of LF, and a situation that probably occurs during bacterial infection.

Original languageEnglish (US)
Pages (from-to)723-729
Number of pages7
JournalJournal of Immunology
Issue number2
StatePublished - 1991

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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