Neutrophil-derived trail is a proinflammatory subtype of neutrophil-derived extracellular vesicles | Zendy

Young-Jin Youn | Zendy; Sanjeeb Shrestha | Zendy; Yu-Bin Lee | Zendy; Jun-Kyu Kim | Zendy; Jee Hyun Lee | Zendy; Keun Hur | Zendy; Nanda Maya Mali | Zendy; SungWook Nam | Zendy; Sun-Hwa Kim | Zendy; S. Lee | Zendy; DongKeun Song | Zendy; Hee Kyung Jin | Zendy; Jaesung Bae | Zendy; Chang-Won Hong | Zendy

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Neutrophil-derived trail is a proinflammatory subtype of neutrophil-derived extracellular vesicles

Author(s) -

Young-Jin Youn,

Sanjeeb Shrestha,

Yu-Bin Lee,

Jun-Kyu Kim,

Jee Hyun Lee,

Keun Hur,

Nanda Maya Mali,

SungWook Nam,

Sun-Hwa Kim,

S. Lee,

DongKeun Song,

Hee Kyung Jin,

Jaesung Bae,

Chang-Won Hong

Publication year - 2021

Publication title -

theranostics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.689

H-Index - 97

ISSN - 1838-7640

DOI - 10.7150/thno.51756

Subject(s) - proinflammatory cytokine , neutrophil extracellular traps , inflammation , microbiology and biotechnology , macrophage polarization , microvesicles , chemotaxis , monocyte , immunology , chemistry , macrophage , biology , microrna , in vitro , receptor , biochemistry , gene

Aims: Extracellular vesicles (EVs) are membrane-derived vesicles that mediate intercellular communications. Neutrophils produce different subtypes of EVs during inflammatory responses. Neutrophil-derived trails (NDTRs) are generated by neutrophils migrating toward inflammatory foci, whereas neutrophil-derived microvesicles (NDMVs) are thought to be generated by neutrophils that have arrived at the inflammatory foci. However, the physical and functional characteristics of neutrophil-derived EVs are incompletely understood. In this study, we aimed to investigate the differences between NDTRs and NDMVs. Methods: The generation of neutrophil-derived EVs were visualized by live-cell fluorescence images and the physical characteristics were further analyzed using nanotracking analysis assay, scanning electron microscopic analysis, and marker expressions. Functional characteristics of neutrophil-derived EVs were analyzed using assays for bactericidal activity, monocyte chemotaxis, phenotype polarization of macrophages, and miRNA sequencing. Finally, the effects of neutrophil-derived EVs on the acute and chronic inflammation were examined in vivo . Results: Both EVs share similar characteristics including stimulators, surface marker expression, bactericidal activity, and chemoattractive effect on monocytes via MCP-1. However, the integrin-mediated physical interaction was required for generation of NDTRs whereas NDMV generation was dependent on PI3K pathway. Interestingly, NDTRs contained proinflammatory miRNAs such as miR-1260, miR-1285, miR-4454, and miR-7975, while NDMVs contained anti-inflammatory miRNAs such as miR-126, miR-150, and miR-451a. Although both EVs were easily uptaken by monocytes, NDTRs enhanced proinflammatory macrophage polarization whereas NDMVs induced anti-inflammatory macrophage polarization. Moreover, NDTRs showed protective effects against lethality in a murine sepsis model and pathological changes in a murine chronic colitis model. Conclusion: These results suggest that NDTR is a proinflammatory subtype of neutrophil-derived EVs distinguished from NDMV.

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