Abstract
Neutrophil extracellular traps (NETs) are formed by neutrophils during inflammation. Among other things, these DNA constructs consist of antimicrobial proteins such as lactoferrin and histones. With these properties, NETs capture and destroy invading microorganisms. The carbohydrate polysialic acid (polySia) interacts with both lactoferrin and histones. Previous experiments demonstrated that, in humans, lactoferrin inhibits the release of NET and that this effect is supported by polySia. In this study, we examined the interplay of lactoferrin and polySia in already-formed NETs from bovine neutrophils. The binding of polySia was considered to occur at the lactoferricin (LFcin)-containing domain of lactoferrin. The interaction with the peptide LFcin was studied in more detail using groups of defined polySia chain lengths, which suggested a chain-length-dependent interaction mechanism with LFcin. The LFcin domain of lactoferrin was found to interact with DNA. Therefore, the possibility that polySia influences the integration of lactoferrin into the DNA-structures of NETs was tested by isolating bovine neutrophils and inducing NETosis. Experiments with NET fibers saturated with lactoferrin demonstrated that polySia initiates the incorporation of external lactoferrin in already-loaded NETs. Thus, polySia may modulate the constituents of NET.
Highlights
The immune system is flexible and multifaceted
PolySia can mediate an accumulation of beads in Neutrophil extracellular traps (NETs), and this binding appears to be mediated by the interaction with histones [23]
In the first set of experiments, we investigated whether the naturally occurring form of polysialic acid (polySia) could mediate the accumulation of beads into NET fibers, serving as an anchor molecule
Summary
The immune system is flexible and multifaceted. For instance, its most abundant leucocytes, neutrophil granulocytes, are able to use different mechanisms to combat pathogens [1,2,3]. In addition to phagocytosis and the release of antimicrobial components through degranulation, a beneficial suicide has been described that involves the release of decondensed DNA, which is associated with antimicrobial molecules [4]. The explosive release of the loaded DNA results in the vast spread of a three-dimensional (3D) DNA meshwork that surrounds the pathogens [4,5]. This molecular web is called a neutrophil extracellular trap (NET), as summarized by Brinkmann and Zychlinsky [6]. Since the DNA is equipped with antimicrobial components, such as histones, neutrophil elastase, lactoferrin, lysozyme, and catalase, the trapped pathogens can be efficiently killed [4,5]. One of the main advantages of NET is that these molecules remain at this hot spot; high concentrations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
