Proteomic Pathway Analysis of Monocyte-Derived Exosomes during Surgical Sepsis Identifies Immunoregulatory Functions

Wisler, Jon; Singh, Kiran; McCarty, Adara; Abouhashem, Ahmed S.; Christman, John W.; Sen, Chandan K.

doi:10.1089/sur.2019.051

Cited by 31 publications

(34 citation statements)

References 32 publications

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“…Thus, we can infer that monocyte-derived exosomes not only promote the aggregation of monocytes to endothelial cells to cope with PAMPs, but also control excessive inflammatory response by inhibiting the chemotaxis of neutrophils. In addition, proteomic analysis demonstrated that exosomes derived from LPS-stimulated monocytes contain protein networks with potential immunosuppressive patterns ( Wisler et al, 2020 ). These exosomes reduce LPS-induced TNF-α release from recipient monocytes ( Wisler et al, 2020 ), which suggests a exosomal negative feedback mode of monocyte limiting self-overactivation ( Figure 7 ).…”

Section: Effects Of Exosomes On Immune Cells In Sepsismentioning

confidence: 99%

“…In addition, proteomic analysis demonstrated that exosomes derived from LPS-stimulated monocytes contain protein networks with potential immunosuppressive patterns (Wisler et al, 2020). These exosomes reduce LPS-induced TNF-α release from recipient monocytes (Wisler et al, 2020), which suggests a exosomal negative feedback mode of monocyte limiting self-overactivation (Figure 7).…”

Section: Monocytementioning

confidence: 99%

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Exosome: The Regulator of the Immune System in Sepsis

et al. 2021

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Sepsis is a syndrome comprised of a series of life-threatening organ dysfunctions caused by a maladjusted body response to infection with no effective treatment. There is growing evidence that the immune system plays a core role in sepsis. Pathogens cause abnormal host immune response and eventually lead to immunosuppression, which is an important cause of death in patients with sepsis. Exosomes are vesicles derived from double invagination of plasma membrane, associating with immune responses closely. The cargos delivered by exosomes into recipient cells, especially immune cells, effectively alter their response and functions in sepsis. In this review, we focus on the effects and mechanisms of exosomes on multiple immune cells, as well as the role of immune cell-derived exosomes in sepsis. This is helpful for us to have an in-depth understanding of the mechanism of immune disorders in sepsis. Exosomes is also expected to become a novel target and therapeutic approach for sepsis.

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Section: Effects Of Exosomes On Immune Cells In Sepsismentioning

confidence: 99%

Section: Monocytementioning

confidence: 99%

Exosome: The Regulator of the Immune System in Sepsis

et al. 2021

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“…In fact, during the development of sepsis, endogenous EVs undergo fluctuations in both relative quantities and functional effects, making them integral in the progression of pathophysiological conditions. [60][61][62][63] Specifically, in sepsis and subsequent organ damage, endogenous EVs have been implicated as critical immunomodulatory factors that can regulate inflammation, [64][65][66][67][68][69][70][71][72][73] coagulation, [74][75][76][77][78][79][80][81][82] apoptosis, [83] and vascular dysfunction. [69,[84][85][86][87][88] The ability of EVs to trigger, amplify, and sometimes suppress immune responses during disease can be attributed to the presence of distinct membranous proteins or lipids (e.g., phosphatidylserine (PS), integrins, major histocompatibility complexes) and to differential lu-minal cargo (e.g., miRNAs, proteins).…”

Section: Endogenous Roles Of Evs In Sepsismentioning

confidence: 99%

Therapeutic Potential of Extracellular Vesicles for Sepsis Treatment

Kronstadt

Pottash

Levy

et al. 2021

Advanced Therapeutics

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Sepsis is a deadly condition lacking a specific treatment despite decades of research. This has prompted the exploration of new approaches, with extracellular vesicles (EVs) emerging as a focal area. EVs are nanosized, cell-derived particles that transport bioactive components (i.e., proteins, DNA, and RNA) between cells, enabling both normal physiological functions and disease progression depending on context. In particular, EVs have been identified as critical mediators of sepsis pathophysiology. However, EVs are also thought to constitute the biologically active component of cell-based therapies and have demonstrated anti-inflammatory, anti-apoptotic, and immunomodulatory effects in sepsis models. The dual nature of EVs in sepsis is explored here, discussing their endogenous roles and highlighting their therapeutic properties and potential. Related to the latter component, prior studies involving EVs from mesenchymal stem/stromal cells (MSCs) and other sources are discussed and emerging producer cells that could play important roles in future EV-based sepsis therapies are identified. Further, how methodologies could impact therapeutic development toward sepsis treatment to enhance and control EV potency is described.

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“…Acutely after sepsis, monocyte-derived EV induce functional impairment/immuneparalysis in recipient monocytes, by inhibiting the release of TNF-α [58,59]. Monocytederived EV carry classical monocyte-markers CD14, CD4, CD16, CD163 and CCR5 [60] but not generalised EV marker CD63 [61,62] (Figure 3).…”

Section: Monocytes and Macrophagesmentioning

confidence: 99%

Extracellular Vesicles in Innate Immune Cell Programming

2021

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Extracellular vesicles (EV) are a heterogeneous group of bilipid-enclosed envelopes that carry proteins, metabolites, RNA, DNA and lipids from their parent cell of origin. They mediate cellular communication to other cells in local tissue microenvironments and across organ systems. EV size, number and their biologically active cargo are often altered in response to pathological processes, including infection, cancer, cardiovascular diseases and in response to metabolic perturbations such as obesity and diabetes, which also have a strong inflammatory component. Here, we discuss the broad repertoire of EV produced by neutrophils, monocytes, macrophages, their precursor hematopoietic stem cells and discuss their effects on the innate immune system. We seek to understand the immunomodulatory properties of EV in cellular programming, which impacts innate immune cell differentiation and function. We further explore the possibilities of using EV as immune targeting vectors, for the modulation of the innate immune response, e.g., for tissue preservation during sterile injury such as myocardial infarction or to promote tissue resolution of inflammation and potentially tissue regeneration and repair.

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Proteomic Pathway Analysis of Monocyte-Derived Exosomes during Surgical Sepsis Identifies Immunoregulatory Functions

Cited by 31 publications

References 32 publications

Exosome: The Regulator of the Immune System in Sepsis

Exosome: The Regulator of the Immune System in Sepsis

Therapeutic Potential of Extracellular Vesicles for Sepsis Treatment

Extracellular Vesicles in Innate Immune Cell Programming

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