Immune System Modifications Induced in a Mouse Model of Chronic Exposure to<sup>90</sup>Sr

Synhaeve, Nicholas; Musilli, Stefania; Stéfani, Johanna; Nicolas, Nour; Delissen, Olivia; Dublineau, Isabelle; Bertho, Jean-Marc

doi:10.1667/rr14014.1

Cited by 6 publications

(9 citation statements)

References 284 publications

(502 reference statements)

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“…Human and rats have shared similar immune response process, therefore, rats are often used as research models when studying immune responses [4, 47]. Our experimental results revealed that AF could protect lung tissue from cold-exposed inflammation by inhibiting C3/BCR/NF-κB in rats, still, whether there is similar reaction in human body needs further research evidence.…”

Section: Discussionmentioning

confidence: 70%

Amentoflavone ameliorates cold stress-induced inflammation in lung by suppression of C3/BCR/NF-κB pathways

Zhao

Huang

2019

BMC Immunol

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BackgroundCold stress, which may lead to local and systemic injury, is reported to be related to the immune system, especially the complement system. At present, the lack of effective treatment is a critical issue. Amentoflavone (AF), which can inhibit cold stress-induced inflammation in lung by multiple mechanisms, is the main therapeutic ingredient in plants of the genus Selaginella.ResultsIn the current study, we found that cold could induce lung inflammation related to the complement system and its downstream pathways. AF treatment significantly inhibited lung inflammation from cold exposure. We presented evidence that AF can bind to complement component 3 (C3) to regulate inflammation-related pathways involving Lck/Yes novel tyrosine kinase (Lyn), protein kinase B (Akt), nuclear factor-κB (NF-κB) and immune factors. Moreover, 30 mg/kg of AF caused significantly greater improvement than 15 mg/kg in reducing the level of C3 in lung tissue.ConclusionsAF can protect lung tissue from cold exposure. The protective effect may be achieved by inhibition of C3 and negative regulation of the B cell receptor (BCR)/NF-κB signaling pathways and high mobility group box 1 (HMGB1), which ultimately ameliorates the inflammatory response.

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Section: Discussionmentioning

confidence: 70%

Amentoflavone ameliorates cold stress-induced inflammation in lung by suppression of C3/BCR/NF-κB pathways

Zhao

Huang

2019

BMC Immunol

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“…These observed effects remains limited in range but such changes in 90 Sr-exposed BMSCs accumulated in bone tissue may explain some of the previously observed health effects of chronic 90 Sr ingestion. In fact, we previously observed a change in bone physiology towards bone resorption 9 and a modification in immune response that could be linked to B cell differentiation in the bone marrow 10 . Additionally, studies in humans suggested decreased hematopoiesis and an altered immune status after internal contamination with 90 Sr together with a decreased bone remodeling rate 7 8 .…”

Section: Discussionmentioning

confidence: 98%

“…A decreased bone remodeling rate was also observed in this population 8 . In addition, we demonstrated an increased bone resorption 9 and a reduced immune response to a vaccine challenge 10 in mice exposed to 90 Sr through ingestion for 20 weeks. However, the mechanisms underlying these health effects remain unclear.…”

mentioning

confidence: 82%

DNA damage induced by Strontium-90 exposure at low concentrations in mesenchymal stromal cells: the functional consequences

Musilli¹,

Nicolas²,

Ali³

et al. 2017

Sci Rep

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90Sr is one of the radionuclides released after nuclear accidents that can significantly impact human health in the long term. 90Sr accumulates mostly in the bones of exposed populations. Previous research has shown that exposure induces changes in bone physiology both in humans and in mice. We hypothesize that, due to its close location with bone marrow stromal cells (BMSCs), 90Sr could induce functional damage to stromal cells that may explain these biological effects due to chronic exposure to 90Sr. The aim of this work was to verify this hypothesis through the use of an in vitro model of MS5 stromal cell lines exposed to 1 and 10 kBq.mL−1 of 90Sr. Results indicated that a 30-minute exposure to 90Sr induced double strand breaks in DNA, followed by DNA repair, senescence and differentiation. After 7 days of exposure, MS5 cells showed a decreased ability to proliferate, changes in cytokine expression, and changes in their ability to support hematopoietic progenitor proliferation and differentiation. These results demonstrate that chronic exposure to a low concentration of 90Sr can induce functional changes in BMSCs that in turn may explain the health effects observed in following chronic 90Sr exposure.

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“…Scenarios that might result in inappropriate bone marrow exposures include nuclear or radiological emergencies, such as the detonation of a 'dirty bomb', which could result in not only acute external irradiation, but also the risk of internal contamination from the inhalation and/or ingestion of radioactive particulates (Shin and Kim 2009;Rump et al 2018). Documentation of the specific effects of internal radioisotope incorporation on the hematopoietic system is sparse (Synhaeve et al 2016;Burdo et al 2018) and, more importantly, the effects from a combined injury of both external irradiation and internal contamination are, as far as we aware, unknown. Therefore, as part of the work initially performed by the University of Rochester Center for Medical Countermeasures against Radiation, we investigated the effects of combined internal and external exposures on the hematopoietic system of the mouse.…”

Section: Introductionmentioning

confidence: 99%

Acute and late effects of combined internal and external radiation exposures on the hematopoietic system

Calvi

Frisch

Kingsley

et al. 2019

International Journal of Radiation Biology

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Purpose: Incidents, such as nuclear facility accidents and the release of a 'dirty bomb', might result in not only external irradiation of personnel, but additional internal exposures through concomitant inhalation and/or ingestion of radioactive particulates. The purpose of this study was to define the impact of such a combination of radiation injuries on the hematopoietic niche. Material and methods: To assess changes in the murine hematopoietic system, we used a combined exposure of total body irradiation (TBI, 6 Gy) followed immediately by an internal (intraperitoneal) administration of 100 mCi of soluble 137 Cs. We then evaluated acute survival in combined versus single modality exposure groups, as well as assessing hematopoietic function at 12 and 26 week time points. Results: Acutely, the combination of external and internal exposures led to an unexpected delay in excretion of 137 Cs, increasing the absorbed dose in the combined exposure group and leading to mortality from an acute hematopoietic syndrome. At 12 weeks, all exposure paradigms resulted in decreased numbers of phenotypic hematopoietic stem cells (HSCs), particularly the short-term HSCs (ST-HSC); long-term HSCs (LT-HSC) were depleted only in the internal and combined exposure groups. At 26 weeks, there was significant anemia in both the TBI alone and combined exposure groups. There were decreased numbers in both the LT-and ST-HSCs and decreased functionality, as measured by competitive repopulation, was seen in all radiation groups, with the greatest effects seen in the internal and combined exposure groups. Conclusions: Our data indicate that a combined injury of sublethal external irradiation with internal contamination induces significant and persistent changes in the hematopoietic system, as may have been predicted from the literature and our own group's findings. However, a novel observation was that the combined exposure led to an alteration in the excretion kinetics of the internal contamination, increasing the acute effects beyond those anticipated. As a result, we believe that a combined exposure poses a unique challenge to the medical community during both the acute and, possibly, delayed recovery stages.

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Immune System Modifications Induced in a Mouse Model of Chronic Exposure to⁹⁰Sr

Cited by 6 publications

References 284 publications

Amentoflavone ameliorates cold stress-induced inflammation in lung by suppression of C3/BCR/NF-κB pathways

Amentoflavone ameliorates cold stress-induced inflammation in lung by suppression of C3/BCR/NF-κB pathways

DNA damage induced by Strontium-90 exposure at low concentrations in mesenchymal stromal cells: the functional consequences

Acute and late effects of combined internal and external radiation exposures on the hematopoietic system

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Immune System Modifications Induced in a Mouse Model of Chronic Exposure to90Sr

Cited by 6 publications

References 284 publications

Amentoflavone ameliorates cold stress-induced inflammation in lung by suppression of C3/BCR/NF-κB pathways

Amentoflavone ameliorates cold stress-induced inflammation in lung by suppression of C3/BCR/NF-κB pathways

DNA damage induced by Strontium-90 exposure at low concentrations in mesenchymal stromal cells: the functional consequences

Acute and late effects of combined internal and external radiation exposures on the hematopoietic system

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Immune System Modifications Induced in a Mouse Model of Chronic Exposure to⁹⁰Sr