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Nanoparticles Equipped with α2,8-Linked Sialic Acid Chains Inhibit the Release of Neutrophil Extracellular Traps.

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.

SUBMITTER: Bornhofft KF

PROVIDER: S-EPMC6523985 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Nanoparticles Equipped with α2,8-Linked Sialic Acid Chains Inhibit the Release of Neutrophil Extracellular Traps.

Bornhöfft Kim F KF Viergutz Torsten T Kühnle Andrea A Galuska Sebastian P SP

Nanomaterials (Basel, Switzerland) 20190412 4

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. ...[more]

PMID: 31013834

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Project description:Trypanosoma brucei brucei trypomastigotes are classical blood parasites of cattle, these stages might become potential targets for circulating polymorphonuclear neutrophils (PMN). We here investigated NETs extrusion and related oxygen consumption in bovine PMN exposed to motile T. b. brucei trypomastigotes in vitro. Parasite exposure induced PMN activation as detected by enhanced oxygen consumption rates (OCR), extracellular acidification rates (ECAR), and production of total and extracellular reactive oxygen species (ROS). Scanning electron microscopy (SEM) showed that co-cultivation of bovine PMN with motile trypomastigotes resulted in NETs formation within 120 min of exposure. T. b. brucei-induced NETs were confirmed by confocal microscopy demonstrating co-localization of extruded DNA with neutrophil elastase (NE) and nuclear histones. Immunofluorescence analyses demonstrated that trypomastigotes induced different phenotypes of NETs in bovine PMN, such as aggregated NETs (aggNETs), spread NETs (sprNETs), and diffuse NETs (diffNETs) with aggNETs being the most abundant ones. Furthermore, live cell 3D-holotomographic microscopy unveiled detailed morphological changes during the NETotic process. Quantification of T. b. brucei-induced NETs formation was estimated by DNA and nuclear area analysis (DANA) and confirmed enhanced NETs formation in response to trypomastigote stages. Formation of NETs does not result in a decrease of T. b. brucei viability, but a decrease of 26% in the number of motile parasites. Referring the involved signaling pathways, trypomastigote-induced NETs formation seems to be purinergic-dependent, since inhibition via NF449 treatment resulted in a significant reduction of T. b. brucei-triggered DNA extrusion. Overall, future studies will have to analyze whether the formation of aggNETs indeed plays a role in the outcome of clinical disease and bovine African trypanosomiasis-related immunopathological disorders, such as increased intravascular coagulopathy and vascular permeability, often reported to occur in this disease.

Dataset Information

Nanoparticles Equipped with α2,8-Linked Sialic Acid Chains Inhibit the Release of Neutrophil Extracellular Traps.

Publications

Nanoparticles Equipped with α2,8-Linked Sialic Acid Chains Inhibit the Release of Neutrophil Extracellular Traps.

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