To study the molecular and cellular mechanisms of radiation-induced lung injury (RILI) in a non-human primate model, Rhesus macaques were irradiated with lethal doses of radiation to the whole thorax. A subset of the irradiated animals was treated with AEOL 10150, a potent catalytic scavenger of reactive oxygen and nitrogen species. Lung tissues were collected at necropsy for molecular and immunohistochemical (IHC) studies. Microarray expression profiling in the irradiated lung tissues identified differentially expressed genes (DEGs) and pathways important in innate immunity. The elevated expression of cytokines (CCL2, CCL11, IL-8), complement factors (CFB, C3), apoptosis-related molecules (p53, PTEN, Bax, p21, MDM2, c-Caspase 3), and adhesion molecules (fibronectin, integrin β6, ICAM-1) were further studied using real-time PCR, Western blot, or IHC. Oxidative stress and pulmonary inflammatory cell infiltration were increased in the irradiated lungs. Treatment with AEOL 10150 significantly decreased oxidative stress and monocyte/macrophage infiltration. Cytokine/chemokine-induced excessive innate immune response after thoracic irradiation plays an important role in RILI. To our knowledge, this is the first study to highlight the role of cytokine/chemokine-induced innate immune responses in radiation-induced pulmonary toxicity in a NHP model.

中文翻译：

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AEOL 10150 减轻非人类灵长类动物肺组织中辐射诱导的先天免疫反应。

为了在非人类灵长类动物模型中研究辐射引起的肺损伤 (RILI) 的分子和细胞机制，恒河猴的整个胸部接受了致死剂量的辐射。一部分受辐射的动物接受了 AEOL 10150 处理，AEOL 10150 是一种活性氧和氮的有效催化清除剂。在尸检时收集肺组织用于分子和免疫组织化学（IHC）研究。受辐射肺组织中的微阵列表达谱鉴定出差异表达基因（DEG）和先天免疫中重要的通路。细胞因子（CCL2、CCL11、IL-8）、补体因子（CFB、C3）、凋亡相关分子（p53、PTEN、Bax、p21、MDM2、c-Caspase 3）和粘附分子（纤连蛋白、使用实时 PCR、蛋白质印迹或 IHC 进一步研究了整合素 β6、ICAM-1）。受辐射的肺部氧化应激和肺部炎症细胞浸润增加。AEOL 10150 治疗可显着减少氧化应激和单核细胞/巨噬细胞浸润。胸部照射后细胞因子/趋化因子诱导的过度先天免疫反应在 RILI 中发挥重要作用。据我们所知，这是第一项强调细胞因子/趋化因子诱导的先天免疫反应在 NHP 模型中辐射诱导的肺毒性中的作用的研究。