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

Youn, Young-Jin; Shrestha, Sanjeeb; Kim, Jun-Kyu; Lee, Yu-Bin; Lee, Jee Hyun; Hur, Keun; Mali, Nanda Maya; Nam, Sung-Wook; Kim, Sun-Hwa; Lee, Sunwoong; Song, Dong‐Keun; Jin, Hee Kyung; Bae, Jong‐Sup; Hong, Chang-Won

doi:10.2139/ssrn.3571290

Cited by 3 publications

(5 citation statements)

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“…Previous study has shown that neutrophil-derived MVs exert anti-inflammatory responses by suppressing the activation of immune cells such as dendritic cells, monocytes, and macrophages. Since MVs are generated from neutrophils in tissues, they are presumably involved in limiting excessive inflammation by suppression of surrounding inflammatory cells [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Previously it was estimated that M0 macrophages treated with neutrophil-derived MVs showed the increased expression of anti-inflammatory markers such as Arg-1, which confirmed the differentiation of M0 macrophages into M2 subsets. This polarization is important for tissue remodeling and immunoregulation [ 32 ]. In our ovine model the anti-inflammatory response of M2 macrophages was involved in the enhanced amount of urea and elevated ratio of urea/nitrite compared to control MDMs cultures.…”

Section: Discussionmentioning

confidence: 99%

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Application of Natural Neutrophil Products for Stimulation of Monocyte-Derived Macrophages Obtained before and after Osteochondral or Bone Injury

2021

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We evaluated the use of some neutrophil products, namely; autologous rabbit antimicrobial neutrophil extract (rANE), heterologous porcine antimicrobial neutrophil extract (pANE), neutrophil degranulation products (DGP) and neutrophil microvesicles (MVs) for stimulation of monocyte-derived macrophages (MDMs) to improve healing. Two animal models were evaluated; the rabbit model for autologous osteochondral transplantation (OT) with application of rabbit ANE, DGP or MVs for MDMs stimulation, and the ovine model of the insertion of a Ti implant with the use of porcine ANE, and ovine DGP or MVs for MDMs stimulation. Macrophage activity was assessed on the basis of free radical generation and arginase activity. We estimated that DGP acted in a pro-inflammatory way both on rabbit and ovine MDMs. On the other hand, MVs acted as anti-inflammatory stimulator on MDMs in both experiments. The response to ANE depended on origin of extract (autologous or heterologous). Macrophages from rabbits before and after OT stimulated with autologous extract generated lower amount of NO and superoxide, especially after transplantation. In the ovine model of Ti implant insertion, heterologous ANE evoked increased macrophage pro-inflammatory activity. Our study revealed that these neutrophil products could regulate activity of macrophages, polarizing them into pro-or anti-inflammatory phenotypes that could enhance bone and osteochondral tissue healing.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Application of Natural Neutrophil Products for Stimulation of Monocyte-Derived Macrophages Obtained before and after Osteochondral or Bone Injury

2021

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“…NDMPs express extracellular facing proteins that are known to be involved in a variety of important cellular processes and thus can act as bioactive effectors. They have been implicated in a variety of disease processes including host defense [7], inflammatory response [8], and wound healing, lung injury, cancer and sepsis [30,31]. It was found that NDMPs are phagocytosed by THP-1 cells and they have a divergent effect on the immune response by activating phagocytic cells and deactivating bystander cells during sepsis in patients [31].…”

Section: Discussionmentioning

confidence: 99%

Circulating neutrophil-derived microparticles associated with the prognosis of patients with sepsis

Chen

Wang

et al. 2020

Preprint

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Background To investigate the relationship between plasma neutrophil-derived micro-particles (NDMPs) and sepsis patients’ prognosis. Methods Eighty eligible patients were classified as the sepsis and septic shock group according to the international guidelines. Their demographic data, pro-inflammatory mediators (TNF-α, IL-6 and sTREM-1) and sepsis severity assessment index (PCT, APACHE-II scores, MODS scores, mechanical ventilation time, ICU length of stay (LOS) and total hospital length of stay (LOS)) of the post-admission day 1, 3, 5 and 7 were harvested. Their plasma NDMPs were determined with magnetic bead sorting and nanoparticle tracking analyser (NTA). Survival curve against the circulation NDMPs was constructed. Results The NDMPs level was higher in the septic shock patients than in the sepsis patients on the post ICU admission day 1, 3 and 5 ( P < 0.05). The NDMPs levels were significantly increased with a parallel increase of pro-inflammatory mediators and sepsis severity ( P <0.05) as well as mortality. Conclusions Our data suggested that NDMP may be a biomarker of sepsis severity and mortality but how its role on sepsis prognosis warrants further study.

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“…These MVs play a role in tissue injury and organ dysfunction by exerting deleterious procoagulant and proinflammatory effects and inducing endothelial dysfunction [18][19][20][21] . Converging animal and clinical studies have emphasized this deleterious procoagulant role of MVs in sepsis and SS [22][23][24] , whereas a series of unexpected observations have suggested a potential beneficial effect of selected MV subpopulations [25][26][27][28][29] . However, the mechanisms underlying their protective effects are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

“… 18 , 19 , 20 , 21 Converging animal and clinical studies have emphasized this deleterious procoagulant role of MVs in sepsis and SS, 22 , 23 , 24 whereas a series of unexpected observations have suggested a potential beneficial effect of selected MV subpopulations. 25 , 26 , 27 , 28 , 29 However, the mechanisms underlying their protective effects are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Granulocyte microvesicles with a high plasmin generation capacity promote clot lysis and improve outcome in septic shock

Cointe

Vallier

Esnault

et al. 2022

Blood

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Microvesicles (MVs) have previously been shown to exert profibrinolytic capacity, which is increased in patients with septic shock (SS) with a favorable outcome. We therefore hypothesized that the plasmin generation capacity (PGC) could confer to MVs a protective effect supported by their capacity to lyse a thrombus, and we investigated the mechanisms involved. Using a MV-PGC kinetic assay, ELISA and flow cytometry, we found that granulocyte MVs (Gran-MVs) from SS patients display a heterogeneous PGC profile driven by the uPA (urokinase)/uPAR system. In vitro, these MVs lyse a thrombus according to their MV-PGC levels in a uPA/uPAR-dependent manner, as shown in a fluorescent clot lysis test and a lysis front retraction assay. Fibrinolytic activators conveyed by MVs contribute to approximately 30% of the plasma plasminogenolytic capacity of SS patients. In a murine model of SS, the injection of high PGC Gran-MVs significantly improved mouse survival and reduced the number of thrombi in vital organs. This was associated with a modification of the mouse coagulation and fibrinolysis properties toward a more fibrinolytic profile. Interestingly, mouse survival was not improved when soluble uPA was injected. Finally, using a multiplex array on plasma from SS patients, we found that neutrophil elastase correlates with the effect of high-PGC-capacity plasma and modulates the Gran-MV plasmin generation capacity by cleaving uPA-PAI-1 complexes. In conclusion, we show that high PGC level displayed by Gran-MVs reduce thrombus formation and improve survival conferring to Gran-MVs a protective role in a murine model of sepsis.

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

Cited by 3 publications

References 0 publications

Application of Natural Neutrophil Products for Stimulation of Monocyte-Derived Macrophages Obtained before and after Osteochondral or Bone Injury

Application of Natural Neutrophil Products for Stimulation of Monocyte-Derived Macrophages Obtained before and after Osteochondral or Bone Injury

Circulating neutrophil-derived microparticles associated with the prognosis of patients with sepsis

Granulocyte microvesicles with a high plasmin generation capacity promote clot lysis and improve outcome in septic shock

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