Sialylated Cervical Mucins Inhibit the Activation of Neutrophils to Form Neutrophil Extracellular Traps in Bovine in vitro Model
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 circulat...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02478/full |
| _version_ | 1831749938462064640 |
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| author | Kim F. Bornhöfft Kim F. Bornhöfft Alexander Rebl Mary E. Gallagher Torsten Viergutz Kristina Zlatina Colm Reid Sebastian P. Galuska Sebastian P. Galuska |
| author_facet | Kim F. Bornhöfft Kim F. Bornhöfft Alexander Rebl Mary E. Gallagher Torsten Viergutz Kristina Zlatina Colm Reid Sebastian P. Galuska Sebastian P. Galuska |
| author_sort | Kim F. Bornhöfft |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T22:19:07Z |
| format | Article |
| id | doaj.art-12868e37a8d14214972b9d0c521142e1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-21T22:19:07Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-12868e37a8d14214972b9d0c521142e12022-12-21T18:48:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-11-011010.3389/fimmu.2019.02478470747Sialylated Cervical Mucins Inhibit the Activation of Neutrophils to Form Neutrophil Extracellular Traps in Bovine in vitro ModelKim F. Bornhöfft0Kim F. Bornhöfft1Alexander Rebl2Mary E. Gallagher3Torsten Viergutz4Kristina Zlatina5Colm Reid6Sebastian P. Galuska7Sebastian P. Galuska8Institute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyFaculty of Medicine, Institute of Biochemistry, Justus Liebig University Giessen, Giessen, GermanyInstitute of Genome Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyUCD Veterinary Sciences Centre, Dublin, IrelandInstitute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyInstitute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyUCD Veterinary Sciences Centre, Dublin, IrelandInstitute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyFaculty of Medicine, Institute of Biochemistry, Justus Liebig University Giessen, Giessen, GermanyIn 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.02478/fullneutrophil extracellular traps (NET)mucinssialic acidsreproductionsialic acid binding immunoglobulin-like lectins (siglecs)bovine neutrophils |
| spellingShingle | Kim F. Bornhöfft Kim F. Bornhöfft Alexander Rebl Mary E. Gallagher Torsten Viergutz Kristina Zlatina Colm Reid Sebastian P. Galuska Sebastian P. Galuska Sialylated Cervical Mucins Inhibit the Activation of Neutrophils to Form Neutrophil Extracellular Traps in Bovine in vitro Model Frontiers in Immunology neutrophil extracellular traps (NET) mucins sialic acids reproduction sialic acid binding immunoglobulin-like lectins (siglecs) bovine neutrophils |
| title | Sialylated Cervical Mucins Inhibit the Activation of Neutrophils to Form Neutrophil Extracellular Traps in Bovine in vitro Model |
| title_full | Sialylated Cervical Mucins Inhibit the Activation of Neutrophils to Form Neutrophil Extracellular Traps in Bovine in vitro Model |
| title_fullStr | Sialylated Cervical Mucins Inhibit the Activation of Neutrophils to Form Neutrophil Extracellular Traps in Bovine in vitro Model |
| title_full_unstemmed | Sialylated Cervical Mucins Inhibit the Activation of Neutrophils to Form Neutrophil Extracellular Traps in Bovine in vitro Model |
| title_short | Sialylated Cervical Mucins Inhibit the Activation of Neutrophils to Form Neutrophil Extracellular Traps in Bovine in vitro Model |
| title_sort | sialylated cervical mucins inhibit the activation of neutrophils to form neutrophil extracellular traps in bovine in vitro model |
| topic | neutrophil extracellular traps (NET) mucins sialic acids reproduction sialic acid binding immunoglobulin-like lectins (siglecs) bovine neutrophils |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02478/full |
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