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Calcium-Independent Phospholipase A₂ Is Required for Lysozyme Secretion in U937 Promonocytes¹

Institute of Molecular Biology and Genetics, University of Valladolid School of Medicine, Valladolid, Spain

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 A₂ (iPLA₂). 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 PLA₂ 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 iPLA₂ activity. Reconstitution experiments reveal that lysoPC efficiently restores lysozyme secretion in iPLA₂-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 A₂ (cPLA₂). Selective inhibition of cPLA₂ results in a complete abrogation of the arachidonate mobilization response, but has no effect on lysozyme secretion. These results identify iPLA₂-mediated lysoPC production as a necessary component of the molecular machinery leading to lysozyme secretion in U937 cells and rule out a role for cPLA₂ in the response. Collectively, the results demonstrate distinct roles in inflammatory cell signaling for these two intracellular phospholipases.

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