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

Autor:	Youn YJ; Department of Physiology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea., Shrestha S; Department of Physiology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea., Lee YB; Department of Physiology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea., Kim JK; Department of Physiology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea., Lee JH; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea., Hur K; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea., Mali NM; Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea., Nam SW; Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea., Kim SH; Department of Physiology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea., Lee S; Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea., Song DK; Department of Pharmacology, College of Medicine, Hallym University, Chuncheon, 24252, Republic of Korea., Jin HK; Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.; Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, 41944, Republic of Korea., Bae JS; Department of Physiology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.; Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu, 41944, Republic of Korea., Hong CW; Department of Physiology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.
Jazyk:	angličtina
Zdroj:	Theranostics [Theranostics] 2021 Jan 01; Vol. 11 (6), pp. 2770-2787. Date of Electronic Publication: 2021 Jan 01 (Print Publication: 2021).
DOI:	10.7150/thno.51756
Abstrakt:	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. Competing Interests: Competing Interests: The authors have declared that no competing interest exists. (© The author(s).)
Databáze:	MEDLINE
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