Extracellular vesicles mediate low dose ionizing radiation-induced immune and inflammatory responses in the blood

Szatmári, Tünde; Persa, Eszter; Kis, Enikő; Benedek, Anett; Hargitai, Rita; Sáfrány, Géza; Lumniczky, Katalin

doi:10.1080/09553002.2018.1450533

Cited by 39 publications

(33 citation statements)

References 74 publications

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“…Several studies support the involvement of exosomes in mediating RIBE in vivo and in vitro [29,30,37,[53][54][55]. Bystander signals can be communicated through exosomes that can result in functional changes in target cells either by receptor-mediated interactions or by transfer of various bioactive molecules such as proteins, mRNA, miRNA or bioactive lipids carried by exosomes [56,57].…”

Section: Discussionmentioning

confidence: 92%

Phenotypic and Functional Characteristics of Exosomes Derived from Irradiated Mouse Organs and Their Role in the Mechanisms Driving Non-Targeted Effects

Cagatay

Mayah

Mancuso

et al. 2020

IJMS

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Molecular communication between irradiated and unirradiated neighbouring cells initiates radiation-induced bystander effects (RIBE) and out-of-field (abscopal) effects which are both an example of the non-targeted effects (NTE) of ionising radiation (IR). Exosomes are small membrane vesicles of endosomal origin and newly identified mediators of NTE. Although exosome-mediated changes are well documented in radiation therapy and oncology, there is a lack of knowledge regarding the role of exosomes derived from inside and outside the radiation field in the early and delayed induction of NTE following IR. Therefore, here we investigated the changes in exosome profile and the role of exosomes as possible molecular signalling mediators of radiation damage. Exosomes derived from organs of whole body irradiated (WBI) or partial body irradiated (PBI) mice after 24 h and 15 days post-irradiation were transferred to recipient mouse embryonic fibroblast (MEF) cells and changes in cellular viability, DNA damage and calcium, reactive oxygen species and nitric oxide signalling were evaluated compared to that of MEF cells treated with exosomes derived from unirradiated mice. Taken together, our results show that whole and partial-body irradiation increases the number of exosomes, instigating changes in exosome-treated MEF cells, depending on the source organ and time after exposure.

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Section: Discussionmentioning

confidence: 92%

Phenotypic and Functional Characteristics of Exosomes Derived from Irradiated Mouse Organs and Their Role in the Mechanisms Driving Non-Targeted Effects

Cagatay

Mayah

Mancuso

et al. 2020

IJMS

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“…When RIBE is manifested by a release of cytokines, a COX-2-dependent pathway mediated by FasL and TNF-α 50,51 , releasing NO by irradiated cells, triggers the inflammatory response in un-irradiated cells through the p38 pathway 52 . Additionally, several studies have demonstrated that ELV are involved in mediating RIBE in cultured cells 31–34,37–39 and under in vivo conditions 35,36 . These studies suggest that inflammatory responses are involved in mediating RIBE signals.…”

Section: Discussionmentioning

confidence: 99%

Radiation-Induced Bystander Effect is Mediated by Mitochondrial DNA in Exosome-Like Vesicles

Ariyoshi

Miura

Kasai

et al. 2019

Sci Rep

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Exosome-like vesicles (ELV) are involved in mediating radiation-induced bystander effect (RIBE). Here, we used ELV from control cell conditioned medium (CCCM) and from 4 Gy of X-ray irradiated cell conditioned medium (ICCM), which has been used to culture normal human fibroblast cells to examine the possibility of ELV mediating RIBE signals. We investigated whether ELV from 4 Gy irradiated mouse serum mediate RIBE signals. Induction of DNA damage was observed in cells that were treated with ICCM ELV and ELV from 4 Gy irradiated mouse serum. In addition, we treated CCCM ELV and ICCM ELV with RNases, DNases, and proteinases to determine which component of ELV is responsible for RIBE. Induction of DNA damage by ICCM ELV was not observed after treatment with DNases. After treatment, DNA damages were not induced in CCCM ELV or ICCM ELV from mitochondria depleted (ρ0) normal human fibroblast cells. Further, we found significant increase in mitochondrial DNA (mtDNA) in ICCM ELV and ELV from 4 Gy irradiated mouse serum. ELV carrying amplified mtDNA (ND1, ND5) induced DNA damage in treated cells. These data suggest that the secretion of mtDNA through exosomes is involved in mediating RIBE signals.

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“…Radiation-induced bystander effects (RIBE) consists of radiation induced adaptive responses [89], low-dose hypersensitivity [90], damage in DNA such as micronuclei formation, mutations, sister chromatid exchanges, modified gene expression, alteration in the miRNA profile, induced oxidative stress, and cell death [10,11,91,92,93,94,95]. RIBE emerge in non-irradiated cells that have received damaging signals from directly irradiated cells via intercellular communication [96,97,98,99].…”

Section: Evs and Radiationmentioning

confidence: 99%

“…However, data on radiation-induced changes in EV content is limited [9,10,17,91]. It was demonstrated that EV mediated miRNA (e.g., miR-21, miR-34c) transfer plays important role in RIBE [9,10,11], and proteins could also be important [110].…”

Section: Evs and Radiationmentioning

confidence: 99%

Extracellular Vesicles in Modifying the Effects of Ionizing Radiation

Szatmári¹,

Hargitai²,

Sáfrány³

et al. 2019

IJMS

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Extracellular vesicles (EVs) are membrane-coated nanovesicles actively secreted by almost all cell types. EVs can travel long distances within the body, being finally taken up by the target cells, transferring information from one cell to another, thus influencing their behavior. The cargo of EVs comprises of nucleic acids, lipids, and proteins derived from the cell of origin, thereby it is cell-type specific; moreover, it differs between diseased and normal cells. Several studies have shown that EVs have a role in tumor formation and prognosis. It was also demonstrated that ionizing radiation can alter the cargo of EVs. EVs, in turn can modulate radiation responses and they play a role in radiation-induced bystander effects. Due to their biocompatibility and selective targeting, EVs are suitable nanocarrier candidates of drugs in various diseases, including cancer. Furthermore, the cargo of EVs can be engineered, and in this way they can be designed to carry certain genes or even drugs, similar to synthetic nanoparticles. In this review, we describe the biological characteristics of EVs, focusing on the recent efforts to use EVs as nanocarriers in oncology, the effects of EVs in radiation therapy, highlighting the possibilities to use EVs as nanocarriers to modulate radiation effects in clinical applications.

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Extracellular vesicles mediate low dose ionizing radiation-induced immune and inflammatory responses in the blood

Abstract: Low and high dose effects overlapped both in EV-mediated alterations in signaling pathways leading to RIBE and in their systemic manifestations.

Cited by 39 publications

References 74 publications

Phenotypic and Functional Characteristics of Exosomes Derived from Irradiated Mouse Organs and Their Role in the Mechanisms Driving Non-Targeted Effects

Phenotypic and Functional Characteristics of Exosomes Derived from Irradiated Mouse Organs and Their Role in the Mechanisms Driving Non-Targeted Effects

Radiation-Induced Bystander Effect is Mediated by Mitochondrial DNA in Exosome-Like Vesicles

Extracellular Vesicles in Modifying the Effects of Ionizing Radiation

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