Abstract
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.
Highlights
When sperm enter the female reproductive tract an immune response is initiated and polymorphonuclear neutrophils (PMNs) are recruited [1, 2]
We firstly analyzed the range of Sialic acid-binding immunoglobulin-like lectins (Siglec) in isolated bovine PMNs by Real- Time quantitative Polymerase Chain Reaction (RT-qPCR)
Most bacteria and spermatozoa are eliminated via phagocytosis and probably degranulation of antimicrobial peptides/proteins in addition to the release of reactive oxygen species (ROS) damage spermatozoa
Summary
When sperm enter the female reproductive tract an immune response is initiated and polymorphonuclear neutrophils (PMNs) are recruited [1, 2]. The formation of neutrophil extracellular traps (NETs) can be activated [1, 2]. These molecular traps are mainly targeted against invading pathogens and their mechanism of action includes trapping and killing instruments [4,5,6]. Since the DNA is loaded with high amounts of antimicrobial biomolecules, such as histones, lactoferrin, neutrophil elastases, and antimicrobial peptides, the trapped pathogens can be efficiently eliminated. Several of these antimicrobial molecules are toxic for endogenous cells. Throughout the body a tight control of neutrophil activation is required to regulate the NET response
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