Endogenous Microparticles Drive the Proinflammatory Host Immune Response in Severely Injured Trauma Patients

Balvers, Kirsten; Curry, Nicola; Kleinveld, Derek J. B.; Böing, Anita N.; Nieuwland, Rienk; Goslings, J. Carel; Juffermans, Nicole P.

doi:10.1097/shk.0000000000000321

Cited by 33 publications

(34 citation statements)

References 26 publications

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“…In an animal model of ischemia reperfusion injury, EVs from endothelium and inflammatory cells are shed into the circulation, which can subsequently promote neutrophil migration [19]. Moreover, we showed in an earlier investigation that in trauma patients endogenously circulating EVs can induce an inflammatory host response [20]. As the EVs in this study are derived from allogenic blood, inflammation may have been induced allogenously, but the EVs may also have caused an endogenous host response.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles from Red Blood Cell Products Induce a Strong Pro-Inflammatory Host Response<b>, </b> Dependent on Both Numbers and Storage Duration

Straat

Böing²,

Boer

et al. 2015

Transfus Med Hemother

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Background: Transfusion of red blood cells (RBCs) is associated with adverse outcome, but the causative factor is unknown. Extracellular vesicles (EVs) have pro-inflammatory properties. We hypothesized that EVs released from both fresh and stored RBC products can induce a host inflammatory response in a dose-dependent manner. Methods: Whole blood was incubated with supernatant from RBC units stored for different time periods, either containing (different numbers of) EVs or depleted from EVs. Results: Incubation with both fresh and stored supernatant containing EVs induced a strong host response with production of TNF, IL-6 and IL-8. In supernatant depleted from EVs, this host response was completely abrogated. IL-10 levels were not affected. EV-induced host response was both dependent on the number of EVs as well as on storage time. Conclusions: EVs from both fresh and stored RBC units illicit a strong inflammatory host response in recipients and may therefore contribute to adverse outcome of RBC transfusion.

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Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles from Red Blood Cell Products Induce a Strong Pro-Inflammatory Host Response<b>, </b> Dependent on Both Numbers and Storage Duration

Straat

Böing²,

Boer

et al. 2015

Transfus Med Hemother

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“…Additionally, trauma is characterized by a pro-inflammatory response coinciding with a decreased ability to respond to bacterial antigens. In trauma patients, addition of EVs has been shown to restore cellular reactivity to LPS in an ex vivo design [26]. Whether EVs can be used to “boost” the immune system during a state of reduced host immune response needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, EVs regulate the host response in trauma. The reduced immune response towards endotoxin challenge in trauma is associated with low levels of circulating EVs in trauma compared to controls [26]. The host response to endotoxin was restored by the addition of EVs, suggesting that these EVs drive the synthesis of pro-inflammatory cytokines in response to LPS [26].…”

Section: Inflammatory Effects Of Extracellular Vesicles Evsmentioning

confidence: 99%

“…The reduced immune response towards endotoxin challenge in trauma is associated with low levels of circulating EVs in trauma compared to controls [26]. The host response to endotoxin was restored by the addition of EVs, suggesting that these EVs drive the synthesis of pro-inflammatory cytokines in response to LPS [26]. Most circulating endogenous EVs are derived from platelets, suggesting that platelets are the most important source of EVs involved in host response post-injury.…”

Section: Inflammatory Effects Of Extracellular Vesicles Evsmentioning

confidence: 99%

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The Ability of Extracellular Vesicles to Induce a Pro-Inflammatory Host Response

Hezel

Nieuwland

Bruggen

et al. 2017

IJMS

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Extracellular vesicles (EVs) can modulate the host immune response, executing both pro- and anti-inflammatory effects. As EVs increasingly gain attention as potential carriers for targeted gene and drug delivery, knowledge on the effects of EVs on the host immune response is important. This review will focus on the ability of EVs to trigger a pro-inflammatory host response by activating target cells. The overall view is that EVs can augment an inflammatory response, thereby potentially contributing to organ injury. This pro-inflammatory potential of EVs may hamper its use for therapeutic drug delivery. Whether removal of EVs as a means to reduce a pro-inflammatory or pro-coagulant response during hyper-inflammatory conditions is beneficial remains to be determined. Prior to any proposed therapeutic application, there is a need for further studies on the role of EVs in physiology and pathophysiology using improved detection and characterization methods to elucidate the roles of EVs in inflammatory conditions.

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“…It is generally recognized that accurate determination of microparticle concentration with flow cytometric methods is problematic [51–53]. Flow cytometric methods have limitations in cases where microvesicles form aggregates or complexes with each other or with cells.…”

Section: Platelet Quality From the Perspective Of Productionmentioning

confidence: 99%

Could Microparticles Be the Universal Quality Indicator for Platelet Viability and Function?

Maurer‐Spurej

Chipperfield

2016

Journal of Blood Transfusion

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High quality means good fitness for the intended use. Research activity regarding quality measures for platelet transfusions has focused on platelet storage and platelet storage lesion. Thus, platelet quality is judged from the manufacturer's point of view and regulated to ensure consistency and stability of the manufacturing process. Assuming that fresh product is always superior to aged product, maintaining in vitro characteristics should preserve high quality. However, despite the highest in vitro quality standards, platelets often fail in vivo. This suggests we may need different quality measures to predict platelet performance after transfusion. Adding to this complexity, platelets are used clinically for very different purposes: platelets need to circulate when given as prophylaxis to cancer patients and to stop bleeding when given to surgery or trauma patients. In addition, the emerging application of platelet-rich plasma injections exploits the immunological functions of platelets. Requirements for quality of platelets intended to prevent bleeding, stop bleeding, or promote wound healing are potentially very different. Can a single measurable characteristic describe platelet quality for all uses? Here we present microparticle measurement in platelet samples, and its potential to become the universal quality characteristic for platelet production, storage, viability, function, and compatibility.

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Endogenous Microparticles Drive the Proinflammatory Host Immune Response in Severely Injured Trauma Patients

Cited by 33 publications

References 26 publications

Extracellular Vesicles from Red Blood Cell Products Induce a Strong Pro-Inflammatory Host Response<b>, </b> Dependent on Both Numbers and Storage Duration

Extracellular Vesicles from Red Blood Cell Products Induce a Strong Pro-Inflammatory Host Response<b>, </b> Dependent on Both Numbers and Storage Duration

The Ability of Extracellular Vesicles to Induce a Pro-Inflammatory Host Response

Could Microparticles Be the Universal Quality Indicator for Platelet Viability and Function?

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