Lysosomal phospholipase A2 is selectively expressed in alveolar macrophages
Lysosomal phospholipase A2 is selectively expressed in alveolar macrophages
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DOI：
10.1074/jbc.m407834200
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发表时间：
2004-10-08
影响因子：
4.8
通讯作者：
Shayman, JA
中科院分区：
文献类型：
--
作者：
Abe, A;Hiraoka, M;Shayman, JA
肺表面活性剂是由排列在肺泡内的磷脂和蛋白质组成的表面活性剂。表面活性剂通过降低表面张力稳定肺泡容积。之前，我们发现了一种溶酶体磷脂酶A2，称为LPLA2，对磷脂酰胆碱和磷脂酰乙醇胺具有特异性。磷脂酶定位于溶酶体，不依赖钙，酸性pH值最佳，并使神经酰胺转酰基化。在这里，我们证明LPLA2在肺泡巨噬细胞中选择性表达，而不是在腹膜巨噬细胞、外周血单核细胞或其他组织中表达。其他巨噬细胞相关的磷脂酶A2s没有显示出类似的分布。LPLA2具有高比活性，可识别不饱和磷脂酰胆碱作为底物。与野生型小鼠相比，靶向缺失粒细胞巨噬细胞集落刺激因子（GM-CSF）的小鼠肺泡巨噬细胞的溶酶体磷脂酶A2活性降低了6倍，GM-CSF是表面活性剂分解代谢受损的模型。然而，在转基因GM-CSF在表面活性剂蛋白C启动子的控制下作为转基因表达的小鼠中，LPLA2活性和蛋白水平被测量。因此，LPLA2可能是肺泡巨噬细胞降解肺表面活性剂磷脂的主要酶，并可能在表面活性剂代谢紊乱中缺乏。
Lung surfactant is the surface-active agent comprised of phospholipids and proteins that lines pulmonary alveoli. Surfactant stabilizes the alveolar volume by reducing surface tension. Previously, we identified a lysosomal phospholipase A2, termed LPLA2, with specificity toward phosphatidylcholine and phosphatidylethanolamine. The phospholipase is localized to lysosomes, is calcium-independent, has an acidic pH optimum, and transacylates ceramide. Here, we demonstrate that LPLA2 is selectively expressed in alveolar macrophages but not in peritoneal macrophages, peripheral blood monocytes, or other tissues. Other macrophage-associated phospholipase A2s do not show a comparable distribution. LPLA2 is of high specific activity and recognizes disaturated phosphatidylcholine as a substrate. The lysosomal phospholipase A2 activity is six times lower in alveolar macrophages from mice with a targeted deletion of the granulocyte macrophage colony-stimulating factor (GM-CSF), a model of impaired surfactant catabolism, compared with those from wild-type mice. However, LPLA2 activity and protein levels are measured in GM-CSF null mice in which GM-CSF is expressed as a transgene under the control of the surfactant protein C promoter. Thus LPLA2 may be a major enzyme of pulmonary surfactant phospholipid degradation by alveolar macrophages and may be deficient in disorders of surfactant metabolism.