Neutrophil-Derived Extracellular Vesicles: Proinflammatory Trails and Anti-Inflammatory Microvesicles

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 investigated the similarities and differences between neutrophil-derived EV subtypes. Neutrophil-derived EVs shared similar characteristics regarding stimulators, generation mechanisms, and surface marker expression. Both neutrophil-derived EV subtypes exhibited similar functions, such as direct bactericidal activity and induction of monocyte chemotaxis via MCP-1. However, NDTR generation was dependent on the integrin signaling, while NDMV generation was dependent on the PI3K pathway. Although neutrophil-derived EVs showed similar patterns of markers, CD16 was highly expressed in NDMVs whereas PSGL-1 was highly expressed in NDTRs. Interestingly, both subtypes showed different patterns of miRNA expression and were easily phagocytosed by monocytes. NDTRs induced proinflammatory macrophage polarization, whereas NDMVs induced anti-inflammatory macrophage polarization. Moreover, NDTRs but not NDMVs exerted protective effects against sepsis-induced lethality in a murine sepsis model and pathological changes in a murine chronic colitis model. These results suggest a new insight into neutrophil-derived EV subtypes: proinflammatory NDTRs and anti-inflammatory NDMVs.

Keywords: EV, extracellular vesicle, NDMV, neutrophil-derived microvesicle, NDTR, neutrophil-derived trail

Suggested Citation: Suggested Citation

Youn, Young-Jin and Shrestha, Sanjeeb and Kim, Jun-Kyu and Lee, Yu-Bin and Lee, Jee Hyun and Hur, Keun and Mali, Nanda Maya and Nam, Sung-Wook and Kim, Sun-Hwa and Lee, Sunwoong and Song, Dong-Keun and Jin, Hee Kyung and Bae, Jae-sung and Hong, Changwon, Neutrophil-Derived Extracellular Vesicles: Proinflammatory Trails and Anti-Inflammatory Microvesicles. Available at SSRN: https://ssrn.com/abstract=3571290 or http://dx.doi.org/10.2139/ssrn.3571290

This version of the paper has not been formally peer reviewed.