AIBP augments cholesterol efflux from alveolar macrophages to surfactant and reduces acute lung inflammation
AIBP augments cholesterol efflux from alveolar macrophages to surfactant and reduces acute lung inflammation
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DOI：
10.1172/jci.insight.120519
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发表时间：
2018-08-23
期刊：
影响因子：
8
通讯作者：
Miller, Yury I.
中科院分区：
文献类型：
--
作者：
Choi, Soo-Ho;Wallace, Aaron M.;Miller, Yury I.
急性呼吸窘迫综合征（ARDS）的特点是过度的肺部炎症反应。从炎症细胞的质膜中去除多余的胆固醇有助于减少它们的活化。分泌的载脂蛋白A-I结合蛋白（AIBP）已被证明可以增加胆固醇从内皮细胞向血浆脂蛋白HDL的外排。在这里，我们发现AIBP在人肺的炎症细胞中表达，并在吸入LPS的小鼠中分泌到支气管肺泡间隙。AIBP结合表面活性剂蛋白B和肺泡巨噬细胞对钙因子的胆固醇外排增加，钙因子是一种治疗性表面活性剂配方。体外实验中，表面活性剂存在下的AIBP可降低lps诱导的肺泡巨噬细胞p65、ERK1/2和p38磷酸化以及IL-6分泌。在体内，吸入AIBP可显著减少lps诱导的空气中性粒细胞增多、肺泡毛细血管渗漏和IL-6的分泌。这些结果表明，与血浆中的高密度脂蛋白类似，表面活性剂在肺中充当胆固醇受体。此外，肺损伤增加了肺AIBP的表达，这可能有助于促进胆固醇向表面活性剂的外排，减少炎症。
Acute respiratory distress syndrome (ARDS) is characterized by an excessive pulmonary inflammatory response. Removal of excess cholesterol from the plasma membrane of inflammatory cells helps reduce their activation. The secreted apolipoprotein A-I binding protein (AIBP) has been shown to augment cholesterol efflux from endothelial cells to the plasma lipoprotein HDL. Here, we find that AIBP was expressed in inflammatory cells in the human lung and was secreted into the bronchoalveolar space in mice subjected to inhalation of LPS. AIBP bound surfactant protein B and increased cholesterol efflux from alveolar macrophages to calfactant, a therapeutic surfactant formulation. In vitro, AIBP in the presence of surfactant reduced LPS-induced p65, ERK1/2 and p38 phosphorylation, and IL-6 secretion by alveolar macrophages. In vivo, inhalation of AIBP significantly reduced LPS-induced airspace neutrophilia, alveolar capillary leak, and secretion of IL-6. These results suggest that, similar to HDL in plasma, surfactant serves as a cholesterol acceptor in the lung. Furthermore, lung injury increases pulmonary AIBP expression, which likely serves to promote cholesterol efflux to surfactant and reduce inflammation.