Silica Triggers Inflammation and Ectopic Lymphoid Neogenesis in the Lungs in Parallel with Accelerated Onset of Systemic Autoimmunity and Glomerulonephritis in the Lupus-Prone NZBWF1 Mouse.
Silica Triggers Inflammation and Ectopic Lymphoid Neogenesis in the Lungs in Parallel with Accelerated Onset of Systemic Autoimmunity and Glomerulonephritis in the Lupus-Prone NZBWF1 Mouse.
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DOI：
10.1371/journal.pone.0125481
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Pestka JJ
中科院分区：
文献类型：
--
作者：
Bates MA;Brandenberger C;Langohr I;Kumagai K;Harkema JR;Holian A;Pestka JJ
遗传易感性和环境因素影响着人类自身免疫性疾病的发展。职业性接触结晶二氧化硅(CSiO_2)与自身免疫增加有关，包括系统性红斑狼疮(SLE)，但其潜在机制尚不清楚。这项研究的目的是验证这一假设，即早期重复短期接触cSiO_2将调节狼疮易感雌性NZBWF1小鼠的自身免疫潜伏期和严重程度。从9周龄开始，每周鼻腔暴露于cSiO_2(0.25和1.0毫克)4wk，既缩短了潜伏期，又增加了肾小球肾炎的强度。二氧化硅在肺内引起强烈的炎症反应，表现为广泛的血管周围和支气管周围淋巴浆细胞浸润，包括产生免疫球蛋白的浆细胞，以及CD45R+和CD3+淋巴细胞，高度提示异位淋巴组织(ELT)。此外，支气管肺泡灌洗液中免疫球蛋白和细胞因子单核细胞趋化蛋白-1、肿瘤坏死因子-α和IL-6浓度升高。与cSiO_2相关的肾和肺的效应与血浆中自身抗体和促炎细胞因子的剂量依赖性升高相平行。综上所述，cSiO_2诱导的NZBWF1小鼠肺部炎症和异位淋巴样新生与全身炎症和自身免疫反应以及肾脏早期病理结果密切相关。这些发现表明，在遗传上易患系统性红斑狼疮的小鼠呼吸道暴露于结晶二氧化硅后，肺是触发系统性自身免疫和肾小球肾炎的平台。
Genetic predisposition and environmental factors influence the development of human autoimmune disease. Occupational exposure to crystalline silica (cSiO2) has been etiologically linked to increased incidence of autoimmunity, including systemic lupus erythematosus (SLE), but the underlying mechanisms are poorly understood. The purpose of this study was to test the hypothesis that early repeated short-term cSiO2 exposure will modulate both latency and severity of autoimmunity in the lupus-prone female NZBWF1 mouse. Weekly intranasal exposure to cSiO2 (0.25 and 1.0 mg) for 4 wk beginning at 9 wk of age both reduced latency and increased intensity of glomerulonephritis. cSiO2 elicited robust inflammatory responses in the lungs as evidenced by extensive perivascular and peribronchial lymphoplasmacytic infiltration consisting of IgG-producing plasma cells, and CD45R+ and CD3+ lymphocytes that were highly suggestive of ectopic lymphoid tissue (ELT). In addition, there were elevated concentrations of immunoglobulins and the cytokines MCP-1, TNF-α and IL-6 in bronchoalveolar lavage fluid. cSiO2-associated kidney and lung effects paralleled dose-dependent elevations of autoantibodies and proinflammatory cytokines in plasma. Taken together, cSiO2-induced pulmonary inflammation and ectopic lymphoid neogenesis in the NZBWF1 mouse corresponded closely to systemic inflammatory and autoimmune responses as well as the early initiation of pathological outcomes in the kidney. These findings suggest that following airway exposure to crystalline silica, in mice genetically prone to SLE, the lung serves as a platform for triggering systemic autoimmunity and glomerulonephritis.
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影响因子：
3.3
作者：
Brown, Jared M;Pfau, Jean C;Holian, Andrij
通讯作者：
Holian, Andrij
影响因子：
4.4
作者：
Chouchakova, N;Skokowa, J;Gessner, JE
通讯作者：
Gessner, JE
影响因子：
5.5
作者：
Beamer, Celine A.;Migliaccio, Christopher T.;Holian, Andrij
通讯作者：
Holian, Andrij
影响因子：
2.6
作者：
Abujam, B.;Cheekatla, S. S.;Aggarwal, A.
通讯作者：
Aggarwal, A.
DOI：
10.1006/bbrc.1995.2383
发表时间：
1995-09-25
影响因子：
3.1
作者：
CHEN, F;SUN, SC;DEMERS, LM
通讯作者：
DEMERS, LM