Fas-deficient mice have impaired alveolar neutrophil recruitment and decreased expression of anti-KC autoantibody:KC complexes in a model of acute lung injury.

Fas-deficient mice have impaired alveolar neutrophil recruitment and decreased expression of anti-KC autoantibody:KC complexes in a model of acute lung injury.
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缺乏FAS的小鼠在急性肺损伤模型中损害了肺泡嗜中性粒细胞的募集和抗KC自身抗体的表达降低。

DOI:
10.1186/1465-9921-13-91
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发表时间:
2012-10-09
影响因子:
5.8
通讯作者:
Matute-Bello G
Matute-Bello G
中科院分区:
医学2区
文献类型:
--
作者:
Gil S;Farnand AW;Altemeier WA;Gill SE;Kurdowska A;Krupa A;Florence JM;Matute-Bello G

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暴露于机械通气增强了肺损伤,以响应各种刺激,如细菌内毒素(LPS)。Fas/FasL系统是一种具有促凋亡和促炎症双重功能的受体配体系统,与肺损伤的发病机制有关。在这项研究中,我们测试的假设,一个功能性Fas/FasL系统是需要在机械通气小鼠肺损伤的发展。将C57 BL/6(B6)和Fas缺陷型lpr小鼠暴露于气管内PBS,随后进行自主呼吸,或暴露于气管内LPS,随后进行4小时机械通气,潮气量为10 mL/kg,呼吸速率为150次/分钟,吸入氧气为0.21,呼气末正压(PEEP)为3 cm水柱。与B6小鼠相比,lpr小鼠表现出嗜中性粒细胞反应的减弱,如通过BAL中性粒细胞数量和肺髓过氧化物酶活性的减少所测量的。有趣的是,B6和lpr小鼠具有相似的促炎细胞因子浓度,包括CXCL 1(KC),以及相似的渗透性和凋亡测量值。然而,与lpr小鼠相比,B6小鼠在肺中显示出更大的抗KC:KC免疫复合物沉积。我们的结论是,一个功能Fas/FasL系统所需的充分嗜酸性反应,LPS在机械通气小鼠。
Exposure to mechanical ventilation enhances lung injury in response to various stimuli, such as bacterial endotoxin (LPS). The Fas/FasL system is a receptor ligand system that has dual pro-apoptotic and pro-inflammatory functions and has been implicated in the pathogenesis of lung injury. In this study we test the hypothesis that a functioning Fas/FasL system is required for the development of lung injury in mechanically ventilated mice. C57BL/6 (B6) and Fas-deficient lpr mice were exposed to either intra-tracheal PBS followed by spontaneous breathing or intra-tracheal LPS followed by four hours mechanical ventilation with tidal volumes of 10 mL/kg, respiratory rate of 150 breaths per minute, inspired oxygen 0.21 and positive end expiratory pressure (PEEP) of 3 cm of water. Compared with the B6 mice, the lpr mice showed attenuation of the neutrophilic response as measured by decreased numbers of BAL neutrophils and lung myeloperoxidase activity. Interestingly, the B6 and lpr mice had similar concentrations of pro-inflammatory cytokines, including CXCL1 (KC), and similar measurements of permeability and apoptosis. However, the B6 mice showed greater deposition of anti-KC:KC immune complexes in the lungs, as compared with the lpr mice. We conclude that a functioning Fas/FasL system is required for full neutrophilic response to LPS in mechanically ventilated mice.
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