Mechanical ventilation enhances lung inflammation and caspase activity in a model of mouse pneumovirus infection
Mechanical ventilation enhances lung inflammation and caspase activity in a model of mouse pneumovirus infection
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DOI：
10.1152/ajplung.00467.2007
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发表时间：
2009-01-01
影响因子：
4.9
通讯作者：
Matute-Bello, Gustavo
中科院分区：
文献类型：
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作者：
Bem, Reinout A.;van Woensel, Job B. M.;Matute-Bello, Gustavo
Bem RA，货车Woensel JB，Bos AP，Koski A，Faraday AW，Domachowske JB，Rosenberg HF，Martin TR，Matute-Bello G.机械通气增强小鼠肺炎病毒感染模型的肺部炎症和半胱天冬酶活性。Am J Physiol Lung Cell Mol Physiol 296：L46-L56，2009.首次发表于2008年11月7日; doi：10.1152/ajplung.00467.2007。儿童严重呼吸道合胞病毒（RSV）感染可进展为呼吸窘迫和急性肺损伤（ALI）。越来越多的证据表明，机械通气（MV）通过调节宿主对细菌的免疫反应，在ALI的发展中是一个重要的辅助因素。本研究调查MV是否增强宿主对小鼠肺炎病毒（PVM）的反应，PVM是一种小鼠肺炎病毒，已被用作人类RSV感染的模型。BALB/c小鼠鼻内接种PVM菌株J3666感染小鼠或未感染对照小鼠的稀释澄清肺匀浆。接种后4天，对小鼠进行4小时MV（潮气量，10 ml/kg）或允许其自主呼吸。与仅接种PVM的小鼠相比，给予PVM感染的小鼠MV导致支气管肺泡灌洗液中细胞因子巨噬细胞炎性蛋白（MIP）-2，MIP-1 α（CCL 3）和IL-6浓度增加;肺泡毛细血管对高分子量蛋白的通透性增加;肺匀浆中caspase-3活性增加。我们的结论是，MV增强了炎症和半胱天冬酶细胞死亡途径的激活，以响应肺炎病毒感染。我们推测，MV可能有助于RSV感染患者肺损伤的发展。
Bem RA, van Woensel JB, Bos AP, Koski A, Farnand AW, Domachowske JB, Rosenberg HF, Martin TR, Matute-Bello G. Mechanical ventilation enhances lung inflammation and caspase activity in a model of mouse pneumovirus infection. Am J Physiol Lung Cell Mol Physiol 296: L46-L56, 2009. First published November 7, 2008; doi:10.1152/ajplung.00467.2007.-Severe infection with respiratory syncytial virus (RSV) in children can progress to respiratory distress and acute lung injury (ALI). Accumulating evidence suggests that mechanical ventilation (MV) is an important cofactor in the development of ALI by modulating the host immune responses to bacteria. This study investigates whether MV enhances the host response to pneumonia virus of mice (PVM), a mouse pneumovirus that has been used as a model for RSV infection in humans. BALB/c mice were inoculated intranasally with diluted clarified lung homogenates from mice infected with PVM strain J3666 or uninfected controls. Four days after inoculation, the mice were subjected to 4 h of MV (tidal volume, 10 ml/kg) or allowed to breathe spontaneously. When compared with that of mice inoculated with PVM only, the administration of MV to PVM-infected mice resulted in increased bronchoalveolar lavage fluid concentrations of the cytokines macrophage inflammatory protein (MIP)-2, MIP-1 alpha (CCL3), and IL-6; increased alveolar-capillary permeability to high molecular weight proteins; and increased caspase-3 activity in lung homogenates. We conclude that MV enhances the activation of inflammatory and caspase cell death pathways in response to pneumovirus infection. We speculate that MV potentially contributes to the development of lung injury in patients with RSV infection.