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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02478

Sialylated cervical mucins inhibit the activation of neutrophils to form neutrophil extracellular traps in bovine in vitro model

  • 1Leibniz Institute for Farm Animal Biology, Germany
  • 2University of Giessen, Germany
  • 3University College Dublin, Ireland

In order to combat invading pathogens neutrophils can release neutrophil extracellular traps (NETs). However, since NETs can also damage endogenous cells, several control mechanisms for the formation of NETs must work effectively. For instance, neutrophil activation is silenced within blood circulation by the binding of sialylated glycoconjugates to sialic acid binding immunoglobulin-like lectins (Siglecs) on neutrophils. As neutrophils are recruited within the female reproductive tract, after mating, a comparable mechanism may also take place within the bovine cervix to prevent an exaggerated NET formation and thus, infertility. We examined, if the highly glycosylated mucins, which are the major functional fraction of biomolecules in mucus, represent a potential regulator of NET formation. The qPCR data revealed that in polymorphonuclear neutrophils (PMNs) inhibitory Siglecs are the most frequently expressed Siglecs and might be a potential target of sialylated glycans to modulate the activation of PMNs. Remarkably, the addition of bovine cervical mucins significantly inhibited the formation of NET, which had been induced in response to lipopolysaccharides (LPS) or a combination of phorbol myristate acetate (PMA) and ionomycin. The inhibitory effects were independent of the stage of estrous cycle (estrus, luteal and follicular mucins). PMNs retained their segmented nuclei and membrane perforation was prevented. However, the inhibitory effects were diminished, when sialic acids were released under acidic conditions. Comparable results were achieved, when sialic acids were targeted by neuraminidase digestion, indicating a sialic acid dependent inhibition of NET release. Thus, bovine cervical mucins have an anti-inflammatory capability to modulate NET formation and might be further immunomodulatory biomolecules that support fertility.

Keywords: Neutrophil extracellular traps (NET), Mucins, Sialic Acids, Reproduction, Sialic Acid Binding Immunoglobulin-like Lectins, Bovine neutrophils

Received: 15 May 2019; Accepted: 04 Oct 2019.

Copyright: © 2019 Bornhöfft, Rebl, Gallagher, Viergutz, Zlatina, Reid and Galuska. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mx. Colm Reid, University College Dublin, Dublin, Ireland, colm.reid@ucd.ie
Dr. Sebastian P. Galuska, Leibniz Institute for Farm Animal Biology, Dummerstorf, 18196, Germany, galuska.sebastian@fbn-dummerstorf.de