Anionic Pulmonary Surfactant Phospholipids Inhibit Inflammatory Responses from Alveolar Macrophages and U937 Cells by Binding the Lipopolysaccharide-interacting Proteins CD14 and MD-2
Anionic Pulmonary Surfactant Phospholipids Inhibit Inflammatory Responses from Alveolar Macrophages and U937 Cells by Binding the Lipopolysaccharide-interacting Proteins CD14 and MD-2
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DOI：
10.1074/jbc.m109.040832
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发表时间：
2009-09-18
影响因子：
4.8
通讯作者：
Voelker, Dennis R.
中科院分区：
文献类型：
--
作者：
Kuronuma, Koji;Mitsuzawa, Hiroaki;Voelker, Dennis R.
革兰氏阴性菌脂多糖（LPS）是引起急性肺损伤和呼吸窘迫综合征的主要原因。肺表面活性物质作为脂质和蛋白质的复杂混合物分泌到肺的肺泡表面上。表面活性剂磷脂在降低气液界面的表面张力和防止呼吸周期结束时肺泡塌陷方面至关重要。在本研究中，我们确定棕榈酰-油酰-磷脂酰甘油和磷脂酰肌醇，这是肺表面活性物质的次要成分，和合成的二肉豆蔻酰磷脂酰甘油调节肺泡巨噬细胞的炎症反应。阴离子脂质显着抑制LPS诱导的大鼠和人肺泡巨噬细胞和U937细胞系的一氧化氮和肿瘤坏死因子-α的生产，通过减少LPS引起的多种细胞内蛋白激酶的磷酸化。阴离子脂质也有效地减轻炎症时，给药intrichially与LPS攻击的小鼠。结合研究显示棕榈酰-油酰-磷脂酰甘油和Toll样受体4相互作用蛋白CD 14和MD-2之间的高亲和力相互作用。我们的数据清楚地确定了重要的抗炎特性的次要表面活性剂磷脂在肺的环境界面。
Lipopolysaccharide (LPS), derived from Gram-negative bacteria, is a major cause of acute lung injury and respiratory distress syndrome. Pulmonary surfactant is secreted as a complex mixture of lipids and proteins onto the alveolar surface of the lung. Surfactant phospholipids are essential in reducing surface tension at the air-liquid interface and preventing alveolar collapse at the end of the respiratory cycle. In the present study, we determined that palmitoyl-oleoyl-phosphatidylglycerol and phosphatidylinositol, which are minor components of pulmonary surfactant, and synthetic dimyristoylphosphatidylglycerol regulated the inflammatory response of alveolar macrophages. The anionic lipids significantly inhibited LPS-induced nitric oxide and tumor necrosis factor-alpha production from rat and human alveolar macrophages and a U937 cell line by reducing the LPS-elicited phosphorylation of multiple intracellular protein kinases. The anionic lipids were also effective at attenuating inflammation when administered intratracheally to mice challenged with LPS. Binding studies revealed high affinity interactions between the palmitoyl-oleoyl-phosphatidylglycerol and the Toll-like receptor 4-interacting proteins CD14 and MD-2. Our data clearly identify important anti-inflammatory properties of the minor surfactant phospholipids at the environmental interface of the lung.