Immune consequences of exposure to β-pinene oxidation aerosols: adult versus gestational murine models.

IF 8.2 1区 医学 Q1 TOXICOLOGY
Muriel Pichavant, Madjid Djouina, Gwenola Kervoaze, Christophe Waxin, Nicolas Houzel, Emeline Driencourt, Cécile Thiry, Cécile Vignal, Cécile Coeur, Mathilde Body-Malapel
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引用次数: 0

Abstract

Background: While studies demonstrating the adverse effects of air pollution on human health are accumulating, studies on secondary organic aerosol (SOA) are scarce. However, SOA accounts for a significant portion of airborne particulate matter. In particular, pinene biogenic SOA contributes predominantly to SOA loading in the outdoor atmosphere of natural and urban areas and are also emitted indoors because of the presence of terpenes in numerous consumer products. Our aim was to study the immune consequences of acute exposure to β-pinene ozonolysis gaseous and SOA products in mice. This reaction was generated in an atmospheric simulation chamber, and the mice were exposed to the particulate and gaseous products, to the gaseous products only, or to synthetic air 2 h per day for 3 days in real time in a whole-body inhalation chamber. Exposures were performed in adulthood or in utero. Since some adverse effects only occur in individuals weakened by existing immune activation, such as low-grade inflammation, the immune response was measured in the steady state or in a state of moderate systemic inflammation induced by lipopolysaccharide administration.

Results: Exposure of healthy adult mice caused minor immunosuppression in the lungs. However, in adult mice weakened by moderate systemic inflammation, the same exposure conditions revealed that mice exposed to the β-pinene ozonolysis particulate and gaseous products presented deficient pulmonary and systemic immune responses, including excessive recruitment of B lymphocytes, CD4+ T lymphocytes, CD11b+ dendritic cells, inflammatory monocytes and neutrophils in the lungs and defective recruitment of regulatory T cells in the spleen. In offspring exposed to β-pinene ozonolysis products in utero, the LPS-induced upregulation of Ccl2, Cxcl10 and Icam1 mRNA levels in the lungs and the activation of dendritic cells in the spleen were excessive in female mice. The male offspring developed a normal response to moderate systemic inflammation, except for impaired activation of CD4+ T cells and increased activation of CD103+ dendritic cells in the spleen.

Conclusion: In mice, pulmonary and systemic immune reactions in response to moderate systemic inflammation are dysregulated by exposure to common secondary oxidation products, highlighting interest in the role of these neglected atmospheric compounds in immune disease development and susceptibility to infections.

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暴露于β-蒎烯氧化气溶胶的免疫后果:成年小鼠与妊娠小鼠模型。
背景:虽然证明空气污染对人类健康不利影响的研究越来越多,但关于二次有机气溶胶(SOA)的研究却很少。然而,SOA占空气中颗粒物的很大一部分。特别是,蒎烯生物源性SOA主要对自然和城市地区室外大气中的SOA负荷做出贡献,并且由于许多消费品中存在萜烯,也会在室内排放。我们的目的是研究小鼠急性暴露于β-蒎烯臭氧分解气体和SOA产物的免疫后果。该反应是在大气模拟室中产生的,小鼠在全身吸入室中实时暴露于颗粒和气体产物,仅暴露于气体产物或每天2小时的合成空气中,持续3天。暴露在成年期或子宫内进行。由于某些不良反应仅发生在被现有免疫激活削弱的个体中,例如低度炎症,因此在稳定状态或脂多糖诱导的中度全身性炎症状态下测量免疫反应。结果:暴露在健康成年小鼠的肺部引起轻微的免疫抑制。然而,在受到中度全身炎症削弱的成年小鼠中,同样的暴露条件显示,暴露于β-蒎烯臭氧分解颗粒和气体产物的小鼠出现了肺部和全身免疫反应缺陷,包括肺中B淋巴细胞、CD4+ T淋巴细胞、CD11b+树突状细胞、炎性单核细胞和中性粒细胞的过度募集,以及脾脏中调节性T细胞募集缺陷。在子宫内暴露于β-蒎烯臭氧分解产物的后代中,lps诱导的雌性小鼠肺部Ccl2、Cxcl10和Icam1 mRNA水平上调以及脾脏树突状细胞的激活过度。雄性后代除了CD4+ T细胞活化受损和脾脏CD103+树突状细胞活化增加外,对中度全身性炎症反应正常。结论:在小鼠中,暴露于常见的二次氧化产物会导致中度全身性炎症的肺部和全身免疫反应失调,这突出了这些被忽视的大气化合物在免疫疾病发展和感染易感性中的作用。
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来源期刊
CiteScore
15.90
自引率
4.00%
发文量
69
审稿时长
6 months
期刊介绍: Particle and Fibre Toxicology is an online journal that is open access and peer-reviewed. It covers a range of disciplines such as material science, biomaterials, and nanomedicine, focusing on the toxicological effects of particles and fibres. The journal serves as a platform for scientific debate and communication among toxicologists and scientists from different fields who work with particle and fibre materials. The main objective of the journal is to deepen our understanding of the physico-chemical properties of particles, their potential for human exposure, and the resulting biological effects. It also addresses regulatory issues related to particle exposure in workplaces and the general environment. Moreover, the journal recognizes that there are various situations where particles can pose a toxicological threat, such as the use of old materials in new applications or the introduction of new materials altogether. By encompassing all these disciplines, Particle and Fibre Toxicology provides a comprehensive source for research in this field.
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