Calcium-independent phospholipase A2 is required for lysozyme secretion in U937 promonocytes
Calcium-independent phospholipase A2 is required for lysozyme secretion in U937 promonocytes
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DOI：
10.4049/jimmunol.170.10.5276
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发表时间：
2003-05-15
影响因子：
4.4
通讯作者：
Balsinde, J
中科院分区：
文献类型：
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作者：
Balboa, MA;Sáez, Y;Balsinde, J
作为它们在免疫系统中的监视功能的一部分，单核细胞/巨噬细胞向细胞外介质分泌大量的杀菌酶溶菌酶。我们在此报道，激活的U937前单核细胞的溶菌酶分泌依赖于功能性钙非依赖性磷脂酶A（2）（iPLA（2））。通过溴烯醇内酯或通过用特异性反义寡核苷酸处理来抑制酶导致细胞向细胞外介质分泌溶菌酶的能力降低。钙非依赖性PLA（2）主要负责维持细胞内溶血磷脂酰胆碱（lysoPC）水平的稳态，如iPLA（2）活性缺陷细胞中该代谢物水平的显著降低所示。重组实验表明，lysoPC有效地恢复了iPLA（2）缺陷细胞中的溶菌酶分泌，而其他溶血磷脂，包括溶血磷脂酸，溶血磷脂酰丝氨酸和溶血磷脂酰乙醇胺，则没有影响。在活化的U937细胞中，花生四烯酸的动员受胞质磷脂酶A（2）（cPLA（2））的控制。选择性抑制cPLA（2）导致花生四烯酸动员反应完全消失，但对溶菌酶分泌没有影响。这些结果表明，iPLA（2）介导的lysoPC产生是U937细胞中导致溶菌酶分泌的分子机制的必要组成部分，并排除了cPLA（2）在反应中的作用。总的来说，结果证明了这两种细胞内磷脂酶在炎症细胞信号传导中的不同作用。
As a part of their surveillance functions in the immune system, monocytes/macrophages secrete large amounts of the bactericidal enzyme lysozyme to the extracellular medium. We report here that lysozyme secretion in activated U937 promonocytes depends on a functional calcium-independent phospholipase A(2) (iPLA(2)). Inhibition of the enzyme by bromoenol lactone or by treatment with a specific antisense oligonucleotide results in a diminished capacity of the cells to secrete lysozyme to the extracellular medium. Calcium-independent PLA(2) is largely responsible for the maintenance of the steady state of lysophosphatidylcholine (lysoPC) levels within the cells, as manifested by the marked decrease in the levels of this metabolite in cells deficient in iPLA(2) activity. Reconstitution experiments reveal that lysoPC efficiently restores lysozyme secretion in iPLA(2)-deficient cells, whereas other lysophospholipids, including lysophosphatidic acid, lysophosphatidylserine, and lysophosphatidylethanolamine, are without effect. Arachidonic acid mobilization in activated U937 cells is under control of cytosolic phospholipase A(2) (cPLA(2)). Selective inhibition of cPLA(2) results in a complete abrogation of the arachidonate mobilization response, but has no effect on lysozyme secretion. These results identify iPLA(2)-mediated lysoPC production as a necessary component of the molecular machinery leading to lysozyme secretion in U937 cells and rule out a role for cPLA(2) in the response. Collectively, the results demonstrate distinct roles in inflammatory cell signaling for these two intracellular phospholipases.