Alveolar Macrophage Secretory Products Effect Type 2 Pneumocytes Undergoing Hypoxia-Reoxygenation
Alveolar Macrophage Secretory Products Effect Type 2 Pneumocytes Undergoing Hypoxia-Reoxygenation
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DOI：
10.1016/j.athoracsur.2008.07.071
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发表时间：
2008-12-01
影响因子：
4.6
通讯作者：
Mulligan, Michael S.
中科院分区：
文献类型：
--
作者：
McCourtie, Anton S.;Farivar, Alexander S.;Mulligan, Michael S.
背景。肺泡巨噬细胞的激活对于肺缺血再灌注损伤的发展至关重要。肺泡巨噬细胞和 2 型肺细胞会分泌多种促炎介质来应对氧化应激。它们相互作用的方式以及巨噬细胞如何影响肺缺血再灌注损伤中的肺细胞反应尚不清楚。利用缺氧和复氧的体外模型，我们试图确定2型肺细胞对氧化应激的促炎反应是否会被肺泡巨噬细胞分泌产物放大。方法。将培养的肺细胞暴露于对照培养基或来自暴露于缺氧和复氧的培养的巨噬细胞的培养基。随后使肺细胞经历缺氧和复氧，并评估核因子κB的核转位以及炎性细胞因子和趋化因子的分泌。为了检查任何相互的相互作用，我们逆转了实验，将巨噬细胞暴露于条件性肺细胞培养基中。结果。在来自受刺激巨噬细胞的介质存在下，2 型肺细胞产生的促炎介质显着增强。相反，巨噬细胞暴露于条件性肺细胞培养基对随后暴露于缺氧和复氧的巨噬细胞反应具有抑制作用。结论。肺泡巨噬细胞部分通过放大缺氧和复氧的 2 型肺细胞的炎症反应来驱动肺再灌注损伤的发展。
Background. Activation of the alveolar macrophage is centrally important to the development of lung ischemia reperfusion injury. Alveolar macrophages and type 2 pneumocytes secrete a variety of proinflammatory mediators in response to oxidative stress. The manner in which they interact and how the macrophage may influence pneumocyte responses in lung ischemia reperfusion injury is unknown. Utilizing an in vitro model of hypoxia and reoxygenation, we sought to determine if the proinflammatory response of type 2 pneumocytes to oxidative stress would be amplified by alveolar macrophage secretory products.Methods. Cultured pneumocytes were exposed to control media or media from cultured macrophages exposed to hypoxia and reoxygenation. Pneumocytes were subsequently subjected to hypoxia and reoxygenation and assessed for both nuclear translocation of nuclear factor kappa B and inflammatory cytokine and chemokine secretion. To examine for any reciprocal interactions, we reversed the experiment, exposing macrophages to conditioned pneumocyte media.Results. In the presence of media from stimulated macrophages, production of proinflammatory mediators by type 2 pneumocytes was dramatically enhanced. In contrast, exposure of the macrophage to conditioned pneumocyte media had an inhibitory effect on macrophage responses subsequently exposed to hypoxia and reoxygenation.Conclusions. The alveolar macrophage drives the development of lung reperfusion injury in part through amplification of the inflammatory response of type 2 pneumocytes subjected to hypoxia and reoxygenation.