Nephrology Division, Department of Internal Medicine, University of Michigan, USA.
Prog Lipid Res. 2011 Jan;50(1):1-13. doi: 10.1016/j.plipres.2010.10.006. Epub 2010 Nov 11.
A phospholipase A₂ was identified from MDCK cell homogenates with broad specificity toward glycerophospholipids including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. The phospholipase has the unique ability to transacylate short chain ceramides. This phospholipase is calcium-independent, localized to lysosomes, and has an acidic pH optimum. The enzyme was purified from bovine brain and found to be a water-soluble glycoprotein consisting of a single peptide chain with a molecular weight of 45 kDa. The primary structure deduced from the DNA sequences is highly conserved between chordates. The enzyme was named lysosomal phospholipase A₂ (LPLA₂) and subsequently designated group XV phospholipase A₂. LPLA₂ has 49% of amino acid sequence identity to lecithin-cholesterol acyltransferase and is a member of the αβ-hydrolase superfamily. LPLA₂ is highly expressed in alveolar macrophages. A marked accumulation of glycerophospholipids and extensive lamellar inclusion bodies, a hallmark of cellular phospholipidosis, is observed in alveolar macrophages in LPLA₂(-/-) mice. This defect can also be reproduced in macrophages that are exposed to cationic amphiphilic drugs such as amiodarone. In addition, older LPLA₂(-/-) mice develop a phenotype similar to human autoimmune disease. These observations indicate that LPLA₂ may play a primary role in phospholipid homeostasis, drug toxicity, and host defense.
一种具有广泛甘油磷脂特异性的磷脂酶 A₂从 MDCK 细胞匀浆中被鉴定出来，包括磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰丝氨酸和磷脂酰甘油。该磷脂酶具有将短链神经酰胺转酰基化的独特能力。这种磷脂酶是钙离子非依赖性的，定位于溶酶体中，具有酸性 pH 最佳值。该酶从牛脑中纯化出来，发现是一种水溶性糖蛋白，由一条分子量为 45 kDa 的单一肽链组成。从 DNA 序列推导出来的一级结构在脊索动物之间高度保守。该酶被命名为溶酶体磷脂酶 A₂（LPLA₂），随后被指定为 XV 组磷脂酶 A₂。LPLA₂与卵磷脂-胆固醇酰基转移酶有 49%的氨基酸序列同一性，是 αβ-水解酶超家族的成员。LPLA₂在肺泡巨噬细胞中高度表达。在 LPLA₂(-/-) 小鼠的肺泡巨噬细胞中观察到甘油磷脂的明显积累和广泛的板层包涵体，这是细胞磷脂沉积的标志。这种缺陷也可以在暴露于阳离子两亲性药物（如胺碘酮）的巨噬细胞中重现。此外，年老的 LPLA₂(-/-) 小鼠会出现类似于人类自身免疫性疾病的表型。这些观察结果表明，LPLA₂可能在磷脂稳态、药物毒性和宿主防御中发挥主要作用。
