Novel acute hypersensitivity pneumonitis model induced by airway mycosis and high dose lipopolysaccharide.
Novel acute hypersensitivity pneumonitis model induced by airway mycosis and high dose lipopolysaccharide.
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气道真菌病和大剂量脂多糖诱导的新型急性过敏性肺炎模型
DOI：
10.1186/s12931-021-01850-5
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发表时间：
2021-10-10
影响因子：
5.8
通讯作者：
Knight JM
中科院分区：
文献类型：
--
作者：
Zeng Y;Zhang Y;Huang X;Song L;Polsky K;Wu Y;Kheradmand F;Guo Y;Green LK;Corry DB;Knight JM
背景吸入真菌孢子是严重哮喘的一个强有力的危险因素，并在实验中导致小鼠发生气道真菌病和哮喘样疾病。然而，除了真菌孢子，人类同时暴露于其他炎症因子，如脂多糖（LPS），与疾病表达的相关性不确定。为了确定高剂量吸入LPS如何影响由过敏性霉菌尼日尔曲霉（A.方法用A.在两周内给予和不给予1 μg LPS。气道高反应性，气道和肺部炎症细胞的招聘，抗原特异性免疫球蛋白，和组织病理学的变化进行了determined.ResultsIn比较，小鼠只与A。尼日尔，加入LPS（1 μg）。黑色素瘤可消除气道高反应性，并强烈减弱气道嗜酸性粒细胞增多、PAS+杯状细胞和TH 2反应，同时增强TH 1和TH 17细胞向肺的募集。添加LPS导致更严重的，弥漫性肺部炎症与分散，松散形成的实质性肉芽肿，但未能改变真菌诱导的IgE和IgG antibodies.ConclusionsIn对比强烈过敏性肺表型真菌孢子单独诱导，除了相对高剂量的LPS废除哮喘样功能，取代他们与表型更符合急性过敏性肺炎（HP）。这些发现将已经建立的气道真菌病和哮喘之间的联系扩展到HP，并描述了进一步解剖HP病理生理学的可靠模型。
BackgroundInhalation of fungal spores is a strong risk factor for severe asthma and experimentally leads to development of airway mycosis and asthma-like disease in mice. However, in addition to fungal spores, humans are simultaneously exposed to other inflammatory agents such as lipopolysaccharide (LPS), with uncertain relevance to disease expression. To determine how high dose inhalation of LPS influences the expression of allergic airway disease induced by the allergenic moldAspergillus niger(A. niger).MethodsC57BL/6J mice were intranasally challenged with the viable spores ofA. nigerwith and without 1 μg of LPS over two weeks. Changes in airway hyperreactivity, airway and lung inflammatory cell recruitment, antigen-specific immunoglobulins, and histopathology were determined.ResultsIn comparison to mice challenged only withA. niger, addition of LPS (1 μg) toA. nigerabrogated airway hyperresponsiveness and strongly attenuated airway eosinophilia, PAS+ goblet cells and TH2 responses while enhancing TH1 and TH17 cell recruitment to lung. Addition of LPS resulted in more severe, diffuse lung inflammation with scattered, loosely-formed parenchymal granulomas, but failed to alter fungus-induced IgE and IgG antibodies.ConclusionsIn contrast to the strongly allergic lung phenotype induced by fungal spores alone, addition of a relatively high dose of LPS abrogates asthma-like features, replacing them with a phenotype more consistent with acute hypersensitivity pneumonitis (HP). These findings extend the already established link between airway mycosis and asthma to HP and describe a robust model for further dissecting the pathophysiology of HP.
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DOI：
10.1164/rccm.200805-737oc
发表时间：
2009-01-01
影响因子：
24.7
作者：
Denning, David W.;O'Driscoll, B. Ronan;Niven, Robert M.
通讯作者：
Niven, Robert M.
DOI：
10.1165/rcmb.2019-0339oc
发表时间：
2020-08-01
影响因子：
6.4
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Huppe, Carole-Ann;Blais-Lecours, Pascale;Marsolais, David
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DOI：
10.1111/j.1365-2222.2012.03987.x
发表时间：
2012-05
期刊：
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子：
--
作者：
Agbetile J;Fairs A;Desai D;Hargadon B;Bourne M;Mutalithas K;Edwards R;Morley JP;Monteiro WR;Kulkarni NS;Green RH;Pavord ID;Bradding P;Brightling CE;Wardlaw AJ;Pashley CH
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Pashley CH
DOI：
10.1164/ajrccm.159.4.9807085
发表时间：
1999-04-01
影响因子：
24.7
作者：
Dakhama, A;Hegele, RG;Cormier, Y
通讯作者：
Cormier, Y
DOI：
10.1186/1476-9255-8-15
发表时间：
2011-06-23
期刊：
Journal of inflammation (London, England)
影响因子：
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作者：
Abdelsamed HA;Desai M;Nance SC;Fitzpatrick EA
通讯作者：
Fitzpatrick EA