Characterization of the innate immune response to chronic aspiration in a novel rodent model.
Characterization of the innate immune response to chronic aspiration in a novel rodent model.
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DOI：
10.1186/1465-9921-8-87
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发表时间：
2007-11-27
影响因子：
5.8
通讯作者：
Davis RD
中科院分区：
文献类型：
--
作者：
Appel JZ 3rd;Lee SM;Hartwig MG;Li B;Hsieh CC;Cantu E 3rd;Yoon Y;Lin SS;Parker W;Davis RD
虽然慢性吸入与几种肺部疾病有关，但炎症反应尚未得到表征。因此，开发了一种新的慢性吸入啮齿动物模型，以研究肺中产生的先天免疫应答。将胃液或生理盐水滴入大鼠（n = 48）的左肺中，每周一次，持续4、8、12或16周（每组n = 6）。此后，收集支气管肺泡灌洗标本，测定细胞表型和IL-1 α、IL-1 β、IL-2、IL-4、IL-6、IL-10、GM-CSF、IFN-γ、TNF-α和TGF-β的细胞因子浓度。给予胃液而非生理盐水后，组织学标本显示出巨细胞、纤维化、淋巴细胞性细支气管炎和闭塞性细支气管炎的明显证据。与生理盐水相比，用胃液处理后，左肺（处理）的支气管肺泡灌洗标本显示出持续较高的巨噬细胞和T细胞，CD 4：CD 8 T细胞比率增加。与生理盐水相比，胃液抽吸后支气管肺泡灌洗液标本中IL-1 α、IL-1 β、IL-2、TNF-α和TGF-β的浓度升高。这是第一次描述慢性吸入引起的肺部炎症反应。反复吸入事件可引发由巨噬细胞和T细胞组成的炎症反应，与肺中TGF-β、TNF-α、IL-1 α、IL-1 β、IL-2和纤维化增加相关。结合胃液诱导的淋巴细胞性细支气管炎和闭塞性细支气管炎的观察，这些发现进一步支持慢性吸入与肺部疾病（如闭塞性细支气管炎、肺纤维化和哮喘）之间的相关性。
Although chronic aspiration has been associated with several pulmonary diseases, the inflammatory response has not been characterized. A novel rodent model of chronic aspiration was therefore developed in order to investigate the resulting innate immune response in the lung. Gastric fluid or normal saline was instilled into the left lung of rats (n = 48) weekly for 4, 8, 12, or 16 weeks (n = 6 each group). Thereafter, bronchoalveolar lavage specimens were collected and cellular phenotypes and cytokine concentrations of IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, TNF-alpha, and TGF-beta were determined. Following the administration of gastric fluid but not normal saline, histologic specimens exhibited prominent evidence of giant cells, fibrosis, lymphocytic bronchiolitis, and obliterative bronchiolitis. Bronchoalveolar lavage specimens from the left (treated) lungs exhibited consistently higher macrophages and T cells with an increased CD4:CD8 T cell ratio after treatment with gastric fluid compared to normal saline. The concentrations of IL-1alpha, IL-1beta, IL-2, TNF-alpha and TGF-beta were increased in bronchoalveolar lavage specimens following gastric fluid aspiration compared to normal saline. This represents the first description of the pulmonary inflammatory response that results from chronic aspiration. Repetitive aspiration events can initiate an inflammatory response consisting of macrophages and T cells that is associated with increased TGF-beta, TNF-alpha, IL-1alpha, IL-1beta, IL-2 and fibrosis in the lung. Combined with the observation of gastric fluid-induced lymphocyitic bronchiolitis and obliterative bronchiolitis, these findings further support an association between chronic aspiration and pulmonary diseases, such as obliterative bronchiolitis, pulmonary fibrosis, and asthma.
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影响因子：
6.2
作者：
Charpin, JM;Valcke, J;Israël-Biet, D
通讯作者：
Israël-Biet, D
影响因子：
17.3
作者：
Ledson, MJ;Tran, J;Walshaw, MJ
通讯作者：
Walshaw, MJ
影响因子：
6.1
作者：
Kotani, Tohru;Murashima, Yukiko;Takeuchi, Koji
通讯作者：
Takeuchi, Koji
DOI：
10.1007/s00464-001-8251-2
发表时间：
2002-12-01
影响因子：
3.1
作者：
Lau, CL;Palmer, SM;Eubanks, S
通讯作者：
Eubanks, S
影响因子：
6
作者：
Davis, RD;Lau, CL;Palmer, SM
通讯作者：
Palmer, SM