Ischemia/Reperfusion Injury and its Consequences on Immunity and Inflammation

Slegtenhorst, Bendix R.; Dor, Frank J. M. F.; Rodríguez, Héctor Alejandro Céspedes; Voskuil, Floris; Tullius, Stefan G.

doi:10.1007/s40472-014-0017-6

Cited by 96 publications

(64 citation statements)

References 87 publications

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“…Even though exRNA analysis derived from dead cells can be considered as an artifact of cell culture, there are situations where nonapoptotic, immunogenic cell death (ICD) occurs at abnormal frequencies in an organism. These situations include aging 76 , trauma 77 , ischemia-reperfusion injury 78 , infectious diseases and cancer. In the latter, ICD can occur because of the hypoxic inner mass characteristic of solid tumors or following treatment with cytotoxic agents 79 .…”

Section: Discussionmentioning

confidence: 99%

Fragmentation of extracellular ribosomes and tRNAs shapes the extracellular RNAome

Tosar

Segovia

Gámbaro

et al. 2020

Preprint

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A major proportion of extracellular RNAs (exRNAs) do not co-isolate with extracellular vesicles (EVs) and remain in ultracentrifugation supernatants of cell-conditioned medium or mammalian blood serum. However, little is known about exRNAs beyond EVs. We have previously shown that the composition of the nonvesicular exRNA fraction is highly biased toward specific tRNA-derived fragments capable of forming RNase-protecting dimers. To solve the problem of stability in exRNA analysis, we developed RI-SEC-seq: a method based on sequencing the size exclusion chromatography (SEC) fractions of nonvesicular extracellular samples treated with RNase inhibitors (RI). This method revealed dramatic compositional changes in exRNA population when enzymatic RNA degradation was inhibited. We demonstrated the presence of ribosomes and full-length tRNAs in cell-conditioned medium of a variety of mammalian cell lines. Their fragmentation generates some small RNAs that are highly resistant to degradation. The extracellular biogenesis of some of the most abundant exRNAs demonstrates that extracellular abundance is not a reliable input to estimate RNA secretion rates. Finally, we showed that chromatographic fractions containing extracellular ribosomes can be sensed by dendritic cells. Extracellular ribosomes and/or tRNAs could therefore be decoded as damage-associated molecular patterns.

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Section: Discussionmentioning

confidence: 99%

Fragmentation of extracellular ribosomes and tRNAs shapes the extracellular RNAome

Tosar

Segovia

Gámbaro

et al. 2020

Preprint

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“…Indeed, there are many examples of how the deleterious effects of BD (70) and IRI (71) accelerate acute rejection in experimental models and negatively affect long-term graft survival in humans (72). However, while the effects of BD and IRI on organ quality have been studied extensively, investigations into the effect of brain death and ischemia on tolerance induction are extremely limited.…”

Section: Introductionmentioning

confidence: 99%

Organ-specific differences in achieving tolerance

Madariaga¹,

Kreisel

Madsen

2015

Current Opinion in Organ Transplantation

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Purpose of review When it comes to tolerance induction, kidney allografts behave differently from heart allografts which behave differently from lung allografts. Here, we examine how and why different organ allografts respond differently to the same tolerance induction protocol. Recent findings Allograft tolerance has been achieved in experimental and clinical kidney transplantation. However, inducing tolerance in experimental recipients of heart and lung allografts has proven to be more challenging. New protocols being developed in nonhuman primates based on mixed chimerism and co-transplantation of tolerogenic organs may provide mechanistic insights to help overcome these challenges. Summary Tolerance induction protocols that are successful in patients transplanted with “tolerance-prone” organs such as kidneys and livers will most likely not succeed in recipients of “tolerance-resistant” organs such as hearts and lungs. Separate clinical trials using more robust tolerance protocols will be required to achieve tolerance in heart and lung recipients.

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“…Such activation has been associated with thrombotic complications and graft rejection following solid organ transplantation [38, 39]. Moreover, transplantations with lung from traumatic brain injury mice have been shown to develop HMGB1-mediated acute graft rejection [40].…”

Section: Resultsmentioning

confidence: 99%

Nucleic acid scavenging microfiber mesh inhibits trauma-induced inflammation and thrombosis

et al. 2017

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Trauma patients produce a host of danger signals and high levels of damage-associated molecular patterns (DAMPs) after cellular injury and tissue damage. These DAMPs are directly and indirectly involved in the pathogenesis of various inflammatory and thrombotic complications in patients with severe injuries. No effective therapeutic agents for the removal of DAMPs from blood or tissue fluid have been developed. Herein, we demonstrated that nucleic acid binding polymers, e.g., polyethylenimine (PEI) and polyamidoamine dendrimers, immobilized onto electrospun microfiber mesh can effectively capture various DAMPs, such as extracellular DNAs and high mobility group box 1 (HMGB1). Furthermore, treatment with PEI-immobilized microfiber mesh abrogated the ability of DAMPs, released from dead and dying cells in culture or found in patients following traumatic injury, to activate innate immune responses and coagulation in vitro and in vivo. Nucleic acid scavenging microfiber meshes represent an effective strategy to combat inflammation and thrombosis in trauma.

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Ischemia/Reperfusion Injury and its Consequences on Immunity and Inflammation

Cited by 96 publications

References 87 publications

Fragmentation of extracellular ribosomes and tRNAs shapes the extracellular RNAome

Fragmentation of extracellular ribosomes and tRNAs shapes the extracellular RNAome

Organ-specific differences in achieving tolerance

Nucleic acid scavenging microfiber mesh inhibits trauma-induced inflammation and thrombosis

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