Alum, an aluminum-based adjuvant, induces Sjögren's syndrome-like disorder in mice.
Alum, an aluminum-based adjuvant, induces Sjögren's syndrome-like disorder in mice.
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发表时间：
2014-03
影响因子：
3.7
通讯作者：
H. Bagavant;S. Nandula;P. Kaplonek;P. Rybakowska;U. Deshmukh
中科院分区：
文献类型：
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作者：
H. Bagavant;S. Nandula;P. Kaplonek;P. Rybakowska;U. Deshmukh
目的 佐剂诱导的先天免疫反应被怀疑在某些自身免疫性疾病的引发中发挥作用。本研究探讨了明矾（一种铝基佐剂）在诱导小鼠干燥综合征样疾病中的作用。方法 对近交系雌性新西兰混合 (NZM) 2758 品系小鼠注射明矾。对照小鼠用 PBS 进行类似处理。通过测量毛果芸香碱诱导的唾液分泌来监测小鼠的唾液腺功能障碍。通过组织病理学研究颌下腺内淋巴细胞浸润的存在。通过 ELISA 分析 Ro 和 La 蛋白的自身抗体，并通过间接免疫荧光分析抗核抗体 (ANA) 的存在。结果 治疗后八周，与 PBS 处理的小鼠相比，明矾处理的小鼠唾液产量显着减少。这种功能丧失一直持续到20周时实验结束。明矾处理的小鼠唾液腺炎的发生率和严重程度显着更高。尽管明矾和PBS处理组的血清中抗Ro/La自身抗体水平没有差异，但明矾组表现出更高的ANA反应性。结论 在 NZM2758 小鼠中，明矾会诱发类似干燥综合征的疾病，其特征是慢性唾液腺功能障碍和唾液腺内存在淋巴细胞浸润。因此，对于遗传上易患自身免疫性疾病的个体，应密切监测铝基佐剂诱导自身免疫的潜力。
OBJECTIVES Adjuvant-induced innate immune responses have been suspected to play a role in the initiation of certain autoimmune disorders. This study investigates the role of alum, an aluminum-based adjuvant in the induction of Sjögren's syndrome-like disorder in mice. METHODS Inbred, female New Zealand Mixed (NZM) 2758 strain of mice were injected with alum. Control mice were treated similarly with PBS. The mice were monitored for salivary gland dysfunction by measuring pilocarpine-induced salivation. Presence of lymphocytic infiltrates within the submandibular glands was studied by histopathology. Autoantibodies to Ro and La proteins were analysed by ELISA and the presence of anti-nuclear antibodies (ANA) was analysed by indirect immunofluorescence. RESULTS By eight weeks after treatment, the saliva production in the alum-treated mice was significantly decreased in comparison to the PBS-treated mice. This functional loss persisted till the termination of experiments at 20 wks. The incidence and severity of sialoadenitis was significantly higher in the alum-treated mice. Although there were no differences in the levels of anti-Ro/La autoantibodies in sera of alum and PBS-treated groups, the alum group showed higher ANA reactivity. CONCLUSIONS In the NZM2758 mice, alum induces a Sjögren's syndrome-like disorder that is characterised by chronic salivary gland dysfunction and the presence of lymphocytic infiltrates within the salivary glands. Thus, the potential of aluminum-based adjuvants for induction of autoimmunity should be closely monitored in individuals genetically susceptible to developing autoimmune disorders.