Sublethal hyperoxia impairs pulmonary innate immunity
Sublethal hyperoxia impairs pulmonary innate immunity
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DOI：
10.4049/jimmunol.171.2.955
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发表时间：
2003-07-15
影响因子：
4.4
通讯作者：
Paine, R
中科院分区：
文献类型：
--
作者：
Baleeiro, CEO;Wilcoxen, SE;Paine, R
在治疗危重病人时经常需要补充氧气。高氧对肺宿主防御的影响尚不明确。我们假设高氧除了影响肺泡壁屏障功能外，还直接损害肺宿主防御。C57BL/6小鼠在>95% O-2环境中饲养4天，然后返回室内空气。这种暴露不会导致随后返回室内空气的小鼠死亡。将老鼠放在室内空气中作为对照组。小鼠气管内接种肺炎克雷伯菌，随访观察存活情况。在体内高氧4天后，通过支气管肺泡灌洗收集肺泡巨噬细胞（AM）进行离体实验。与室内空气中的感染小鼠相比，暴露于高氧环境中的小鼠肺炎死亡率显著增加。在高氧组中，肺内微生物负荷和感染传播增加，而肺内炎症细胞的积聚受到损害。单独的高氧对AM的数量、生存能力或吞噬乳胶微珠的能力没有影响。然而，在体内高氧后，AM的吞噬作用和革兰氏阴性菌的杀死以及对LPS的反应中tnf - α和IL-6的产生显著降低。体内高氧后AM表面toll样受体-4的表达显著降低。因此，亚致死性高氧增加了革兰氏阴性细菌性肺炎的死亡率，并对AM宿主防御功能有显著的不利影响。由于高浓度补充氧导致AM功能受损可能导致危重患者呼吸机相关性肺炎的高发。
Supplemental oxygen is often required in the treatment of critically ill patients. The impact of hyperoxia on pulmonary host defense is not well-established. We hypothesized that hyperoxia directly impairs pulmonary host defense, beyond effects on alveolar wall barrier function. C57BL/6 mice were kept in an atmosphere of >95% O-2 for 4 days followed by return to room air. This exposure does not lead to mortality in mice subsequently returned to room air. Mice kept in room air served as controls. Mice were intratracheally inoculated with Klebsiella pneumoniae and followed for survival. Alveolar macrophages (AM) were harvested by bronchoalveolar lavage after 4 days of in vivo hyperoxia for ex vivo experiments. Mortality from pneumonia increased significantly in mice exposed to hyperoxia compared with infected mice in room air. Burden of organisms in the lung and dissemination of infection were increased in the hyperoxia group whereas accumulation of inflammatory cells in the lung was impaired. Hyperoxia alone had no impact on AM numbers, viability, or ability to phagocytize latex microbeads. However, following in vivo hyperoxia, AM phagocytosis and killing of Gram-negative bacteria and production of TNF-alpha and IL-6 in response to LPS were significantly reduced. AM surface expression of Toll-like receptor-4 was significantly decreased following in vivo hyperoxia. Thus sublethal hyperoxia increases Gram-negative bacterial pneumonia mortality and has a significant adverse effect on AM host defense function. Impaired AM function due to high concentrations of supplemental oxygen may contribute to the high rate of ventilator-associated pneumonia seen in critically ill patients.