Microvesicle Subsets in Sepsis Due to Community Acquired Pneumonia Compared to Faecal Peritonitis

Lashin, Hazem; Nadkarni, Suchita; Oggero, Silvia; Jones, Hefin; Knight, Julian C.; Hinds, C. J.; Perretti, Mauro

doi:10.1097/shk.0000000000000989

Cited by 28 publications

(45 citation statements)

References 31 publications

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“…Second, the suppression of TNF release by neutrophil-MDM co-culture supernatants, which is abolished by ultracentrifugation, indicates a requirement for complexes of mediators and/or released extracellular vesicles. Microvesicles released from viable neutrophils exert immunosuppressive activity in vitro 27 – 29 and in vivo 9 when highly concentrated and display several phenotypes 30 . However, our observations suggest that two-way communication between the macrophage and neutrophil is required to induce release of the required mediators.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation

et al. 2018

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Apoptotic cells modulate the function of macrophages to control and resolve inflammation. Here, we show that neutrophils induce a rapid and sustained suppression of NF-κB signalling in the macrophage through a unique regulatory relationship which is independent of apoptosis. The reduction of macrophage NF-κB activation occurs through a blockade in transforming growth factor β-activated kinase 1 (TAK1) and IKKβ activation. As a consequence, NF-κB (p65) phosphorylation is reduced, its translocation to the nucleus is inhibited and NF-κB-mediated inflammatory cytokine transcription is suppressed. Gene Set Enrichment Analysis reveals that this suppression of NF-κB activation is not restricted to post-translational modifications of the canonical NF-κB pathway, but is also imprinted at the transcriptional level. Thus neutrophils exert a sustained anti-inflammatory phenotypic reprogramming of the macrophage, which is reflected by the sustained reduction in the release of pro- but not anti- inflammatory cytokines from the macrophage. Together, our findings identify a novel apoptosis-independent mechanism by which neutrophils regulate the mediator profile and reprogramming of monocytes/macrophages, representing an important nodal point for inflammatory control.

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Section: Discussionmentioning

confidence: 99%

Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation

et al. 2018

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“…The “sepsis” diagnosis encompasses patients with a multitude of scenarios by which the microbial invasion develop. To our knowledge, only one recent study compared the role of EVs among subsets of septic patients based on the site of infection 16 .…”

Section: Heterogeneity Versus Standardization: Critical Assessment Ofmentioning

confidence: 99%

“…In at least 14 studies, the septic patients were in the state of shock. It is unknown whether re-analysis of sepsis studies using the new Sepsis-3 definitions for enrollment (and thus redistributing groups) would change their conclusions; new studies selecting patients based on the new Sepsis-3 have been only recently emerging 16 . Interestingly, redistribution of patients according to the Sepsis-3 definition did not affect conclusions drawn in the recent study by Matsumoto et al 19 .…”

Section: Heterogeneity Versus Standardization: Critical Assessment Ofmentioning

confidence: 99%

Extracellular Vesicles as Markers and Mediators in Sepsis

2018

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Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. It remains a highly lethal condition in which current tools for early diagnosis and therapeutic decision-making are far from ideal. Extracellular vesicles (EVs), 30 nm to several micrometers in size, are released from cells upon activation and apoptosis and express membrane epitopes specific for their parental cells. Since their discovery two decades ago, their role as biomarkers and mediators in various diseases has been intensively studied. However, their potential importance in the sepsis syndrome has gained attention only recently. Sepsis and EVs are both complex fields in which standardization has long been overdue. In this review, several topics are discussed. First, we review current studies on EVs in septic patients with emphasis on their variable quality and clinical utility. Second, we discuss the diagnostic and therapeutic potential of EVs as well as their role as facilitators of cell communication via micro RNA and the relevance of micro-organism-derived EVs. Third, we give an overview over the potential beneficial but also detrimental roles of EVs in sepsis. Finally, we focus on the role of EVs in selected intensive care scenarios such as coagulopathy, mechanical ventilation and blood transfusion. Overall, the prospect for EV use in septic patients is bright, ranging from rapid and precise (point-of-care) diagnostics, prevention of harmful iatrogenic interventions, to using EVs as guides of individualized therapy. Before the above is achieved, however, the EV research field requires reliable standardization of the current methods and development of new analytical procedures that can close the existing technological gaps.

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“…Elevated plasma extracellular vesicle concentrations were associated with a lower risk of developing ARDS; this association was seen most strongly in patients admitted to ICU with sepsis. Another group of investigators [23] found that a subset of circulating leukocyte extracellular vesicles expressing α2-macroglobulin (A2MG) were associated with survival in ICU patients with sepsis secondary to pneumonia, but not in patients with sepsis secondary to fecal peritonitis. A2MG-EV treatment in vitro reduced endothelial cell permeability and increased bacterial phagocytosis by neutrophils.…”

Section: Potential Endogenous Protective Effects Of Extracellular Vesmentioning

confidence: 99%

“…Several studies that have investigated the role of extracellular vesicles in acute lung injury and ARDS have been done in animal and in vitro models, although one recent study was done in the ex vivo perfused human lung [12], and there are a few clinical studies as well [13,18,[21][22][23]. Future studies will need to characterize BALF and circulating extracellular vesicles from ARDS patients with regard to the cell of origin, cargo assessment (RNA, protein, organelle content), and their biological effect on human cells and human tissues.…”

Section: Future Directionsmentioning

confidence: 99%

Extracellular Vesicles in ARDS: New Insights into Pathogenesis with Novel Clinical Applications

Mahida

Matsumoto

Matthay

2020

Annual Update in Intensive Care and Emergency Medicine

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Microvesicle Subsets in Sepsis Due to Community Acquired Pneumonia Compared to Faecal Peritonitis

Abstract: Plasma MV profiles vary according to the source of infection. A2MG MV are associated with survival in CAP but not FP. We propose specific MV subsets as novel biomarkers in sepsis and potential effector for some of the actions of experimental therapeutic interventions.

Cited by 28 publications

References 31 publications

Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation

Neutrophils induce macrophage anti-inflammatory reprogramming by suppressing NF-κB activation

Extracellular Vesicles as Markers and Mediators in Sepsis

Extracellular Vesicles in ARDS: New Insights into Pathogenesis with Novel Clinical Applications

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