A biphasic response to silica -: I.: Immunostimulation is restricted to the early stage of silicosis in Lewis rats
A biphasic response to silica -: I.: Immunostimulation is restricted to the early stage of silicosis in Lewis rats
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DOI：
10.1165/rcmb.2003-0284oc
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发表时间：
2004-06-01
影响因子：
6.4
通讯作者：
Sopori, ML
中科院分区：
文献类型：
--
作者：
Langley, RJ;Kalra, R;Sopori, ML
吸入结晶二氧化硅可能会导致急性或慢性矽肺。虽然慢性矽肺与自身免疫性疾病的发病率/加重有关，但慢性矽肺的免疫学影响尚未完全了解。在慢性矽肺动物模型中，Lewis大鼠暴露于过滤空气或二氧化硅(平均粒径1.75um)中，暴露浓度为6.2 mg/m(3)，6h/d，5d/wk，持续6wk，并观察到暴露后27wk。根据二氧化硅负荷、肺组织病理学和免疫学变化，慢性矽肺的发展分为两个不同的阶段。阶段1(暴露后4-28d)以各种组织中二氧化硅沉积为特征，抗体和细胞免疫增强。虽然支气管肺泡灌洗液中含有更多激活的巨噬细胞，但蛋白质和乳酸脱氢酶水平与对照组相当。在第2阶段(大于或等于10wk)，二氧化硅定位于上皮样巨噬细胞，T细胞免疫功能恢复正常，但灌洗液中蛋白质浓度和乳酸脱氢酶活性增加。此外，经二氧化硅处理的动物的肺含有中性粒细胞和淋巴细胞，并在含二氧化硅的上皮样巨噬细胞周围显示肉芽肿改变。因此，在矽肺的早期阶段，二氧化硅会激活免疫系统；然而，肺肉芽肿的进展并不依赖于持续激活的适应性免疫系统。
Inhalation of crystalline silica may lead to acute or chronic silicosis. Although chronic silicosis is associated with increased incidence/exacerbation of autoimmune disorders, the immunologic effects of chronic silicosis are not completely understood. In an animal model of chronic silicosis, Lewis rats were exposed to filtered air or silica (1.75 mum average particle size) at an exposure concentration of 6.2 mg/m(3), 6 h/d, 5 d/wk for 6 wk, and observed up to 27 wk after the exposure. Based on silica burden, lung histopathology, and immunologic changes, two distinct stages were identified in the development of chronic silicosis. Stage 1 (4-28 d after exposure) was characterized by silica deposition in various tissues, and augmented antibody and cellular immunity. Although bronchoalveolar lavage contained an increased number of activated macrophages, protein and lactate dehydrogenase levels were comparable to controls. In Stage 2 (greater than or equal to 10 wk), silica was localized in epithelioid macrophages, and T cell immunity had returned to normal, but the lavage fluids contained increased protein concentration and lactate dehydrogenase activity. Moreover, lungs from silica-treated animals contained neutrophils and lymphocytes, and exhibited granulomatous changes around the silica-containing epithelioid macrophages. Thus, in the early stages of silicosis, silica activates the immune system; however, the progression of lung granulomas does not depend on a continually activated adaptive immune system.