Open Access

The effect of carbohydrate moiety structure on the immunoregulatory activity of lactoferrin in vitro

  • Michał Zimecki1Email author,
  • Jolanta Artym1,
  • Maja Kocięba1,
  • Maria Duk2 and
  • Marian L. Kruzel3
Cellular & Molecular Biology LettersAn International Journal201419:196

https://doi.org/10.2478/s11658-014-0196-2

Received: 26 July 2013

Accepted: 28 April 2014

Published: 12 May 2014

Abstract

The aim of this study was to evaluate the immunoregulatory effects of recombinant human lactoferrin (rhLF) in two in vitro models: (1) the secondary humoral immune response to sheep erythrocytes (SRBC); and (2) the mixed lymphocyte reaction (MLR). We compared the non-sialylated glycoform of rhLF as expressed by glycoengineered Pichia pastoris with one that was further chemically sialylated. In an earlier study, we showed that sialylated rhLF could reverse methotrexate-induced suppression of the secondary immune response of mouse splenocytes to SRBC, and that the phenomenon is dependent on the interaction of lactoferrin (LF) with sialoadhesin (CD169). We found that the immunorestorative activity of sialylated rhLF is also dependent on its interaction with the CD22 antigen, a member of the immunoglobulin superfamily that is expressed by B lymphocytes. We also demonstrated that only sialylated rhLF was able to inhibit the MLR reaction. MLR was inhibited by bovine lactoferrin (bLF), a glycoform that has a more complex glycan structure. Desialylated bLF and lactoferricin, a bLF-derived peptide devoid of carbohydrates, did not express such inhibitory activity. We showed that the interaction of LF with sialic acid receptors is essential for at least some of the immunoregulatory activity of this glycoprotein.

Keywords

Human recombinant lactoferrin CD22 Sialic acid Humoral immune response Mixed lymphocyte reaction CD169 Glycoproteins Immune suppression

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