Abstract
Neutrophils can combat the invasion of pathogens by the formation of neutrophil extracellular traps (NETs). The NET mechanism is not only an effective tool for combating pathogens, but is also associated with diseases. Therefore, NETs are a potential target for combating pathologies, such as cystic fibrosis and thrombosis. We investigated the potential of nanoparticles, which were modified with α2,8-linked sialic acid chains, to modulate NET release during phorbol myristate acetate stimulation. Interestingly, when these nanoparticles were applied, the formation of reactive oxygen species was partly inhibited and the release of NET was counteracted. However, although the release of NET fibers was prevented, the nuclei still lost their characteristic segmented structure and became swollen, indicating that only the release, and not complete activation was suppressed. Intriguingly, coincubation of α2,8-sialylated particles with free sialic acid chains prevented the outlined inhibitory effects. Thus, the sialic acid chains must be attached to a linker molecule to generate an active bioconjugate that is able to inhibit the release of NET.
Highlights
Neutrophil granulocytes are the most abundant leukocytes of the innate immune system representing the first line of defense against invading pathogens [1,2,3]
We investigated the potential of nanoparticles, which were modified with α2,8-linked sialic acid chains, to modulate neutrophil extracellular traps (NETs) release during phorbol myristate acetate stimulation
The sialic acid chains must be attached to a linker molecule to generate an active bioconjugate that is able to inhibit the release of NET
Summary
Neutrophil granulocytes are the most abundant leukocytes of the innate immune system representing the first line of defense against invading pathogens [1,2,3]. ERK1/2 seems to activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by phosphorylation, contributing to the activation of the NADPH oxidase enzyme complex [4,9,13,14,15] This complex produces ROS, which are enzymatically converted to hypochlorous acid (HOCl) by myeloperoxidase [4,9]. Glycans are often terminated with sialic acid residues [25] These sialylated structures can be recognized by immune cells using, for example, sialic acid-binding immunoglobulin–like lectins (siglecs), which are important immunoregulatory elements in vertebrates [26,27,28,29]. The obtained results demonstrate that the release of NETs is inhibited by the application of particles containing α2,8-linked sialic acid chains, indicating that α2,8-sialylated nanoparticles are a tool for manipulating the formation of NET
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