Department of Clinical Medicine, Trinity College Dublin, Dublin, Ireland.
Thoracic Oncology Research Group, St James's Hospital, Dublin, Ireland.
Sci Rep. 2018 Jan 12;8(1):679. doi: 10.1038/s41598-017-19068-1.
Citrullination, or the post-translational deimination of polypeptide-bound arginine, is involved in several pathological processes in the body, including autoimmunity and tumorigenesis. Recent studies have shown that nanomaterials can trigger protein citrullination, which might constitute a common pathogenic link to disease development. Here we demonstrated auto-antibody production in serum of nanomaterials-treated mice. Citrullination-associated phenomena and PAD levels were found to be elevated in nanomaterials -treated cell lines as well as in the spleen, kidneys and lymph nodes of mice, suggesting a systemic response to nanomaterials injection, and validated in human pleural and pericardial malignant mesothelioma (MM) samples. The observed systemic responses in mice exposed to nanomaterials support the evidence linking exposure to environmental factors with the development of autoimmunity responses and reinforces the need for comprehensive safety screening of nanomaterials. Furthermore, these nanomaterials induce pathological processes that mimic those observed in Pleural MM, and therefore require further investigations into their carcinogenicity.
瓜氨酸化，或多肽结合精氨酸的翻译后脱亚精氨酸化，参与体内的几种病理过程，包括自身免疫和肿瘤发生。最近的研究表明，纳米材料可以触发蛋白质瓜氨酸化，这可能构成疾病发展的共同致病联系。在这里，我们证明了纳米材料处理小鼠血清中的自身抗体产生。在纳米材料处理的细胞系以及小鼠的脾脏、肾脏和淋巴结中发现瓜氨酸化相关现象和 PAD 水平升高，提示对纳米材料注射的全身性反应，并在人类胸膜和心包恶性间皮瘤（MM）样本中得到验证。暴露于纳米材料的小鼠中观察到的全身性反应支持了将暴露于环境因素与自身免疫反应发展联系起来的证据，并强调了对纳米材料进行全面安全筛选的必要性。此外，这些纳米材料诱导的病理过程模拟了在胸膜 MM 中观察到的过程，因此需要进一步研究其致癌性。
