A highly conserved host lipase deacylates oxidized phospholipids and ameliorates acute lung injury in mice.
A highly conserved host lipase deacylates oxidized phospholipids and ameliorates acute lung injury in mice.
复制标题
高度保守的宿主脂肪酶使氧化磷脂脱酰并改善小鼠急性肺损伤
作者：
Zou B;Goodwin M;Saleem D;Jiang W;Tang J;Chu Y;Munford RS;Lu M
氧化磷脂具有多种生物活性，其中许多可能是病理性的，但它们如何在体内失活还不完全清楚。在这里，我们提出的证据表明，一个高度保守的宿主脂肪酶，酰氧酰基水解酶（AOAH），可以发挥重要的作用，在减少两个突出的磷脂氧化产物，1-棕榈酰-2-戊二酰-sn-甘油-3-磷酸胆碱和1-棕榈酰-2-（5-氧代戊酰基）-sn-甘油-3-磷酸胆碱的促炎活性。AOAH去除了两种脂质中的sn-2和sn-1酰基链，并降低了它们诱导体外巨噬细胞炎性小体活化和细胞死亡以及小鼠急性肺损伤的能力。除了将革兰氏阴性细菌脂多糖从刺激物转化为抑制物之外，AOAH还可以抑制这些重要的细菌相关分子模式分子，并减少组织炎症和损伤。
Oxidized phospholipids have diverse biological activities, many of which can be pathological, yet how they are inactivated in vivo is not fully understood. Here, we present evidence that a highly conserved host lipase, acyloxyacyl hydrolase (AOAH), can play a significant role in reducing the pro-inflammatory activities of two prominent products of phospholipid oxidation, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine. AOAH removed the sn-2 and sn-1 acyl chains from both lipids and reduced their ability to induce macrophage inflammasome activation and cell death in vitro and acute lung injury in mice. In addition to transforming Gram-negative bacterial lipopolysaccharide from stimulus to inhibitor, its most studied activity, AOAH can inactivate these important danger-associated molecular pattern molecules and reduce tissue inflammation and injury.