Department of Medicine, UCSD, La Jolla, California, USA.
Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
JCI Insight. 2018 Aug 23;3(16). doi: 10.1172/jci.insight.120519.
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.
急性呼吸窘迫综合征（ARDS）的特征是过度的肺部炎症反应。从炎症细胞的质膜中去除过量的胆固醇有助于减少其激活。已表明分泌的载脂蛋白 A-I 结合蛋白（AIBP）可增强内皮细胞向血浆脂蛋白 HDL 的胆固醇流出。在这里，我们发现 AIBP 在人肺中的炎症细胞中表达，并在小鼠吸入 LPS 后分泌到支气管肺泡空间中。AIBP 与表面活性剂蛋白 B 结合，并增加了肺泡巨噬细胞向 calfactant（一种治疗性表面活性剂制剂）的胆固醇流出。在体外，含有表面活性剂的 AIBP 可降低 LPS 诱导的 p65、ERK1/2 和 p38 磷酸化以及肺泡巨噬细胞中 IL-6 的分泌。在体内，吸入 AIBP 可显著减少 LPS 诱导的肺泡中性粒细胞增多、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 HDL 相似，表面活性剂在肺部充当胆固醇受体。此外，肺损伤会增加肺 AIBP 的表达，这可能有助于促进胆固醇向表面活性剂的流出并减少炎症。
