Myeloperoxidase-induced formation of chlorohydrins and lysophospholipids from unsaturated phosphatidylcholines

The formation of lysophosphatidylcholines and chlorohydrins from unsaturated phosphatidylcholines upon the treatment with the myeloperoxidase-hydrogen peroxide-chloride system was evaluated by means of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Lyso-products were primarily found in phosphatidylcholine samples containing highly unsaturated fatty acid residues such as arachidonic or docosahexenoic acid. On the other hand, chlorohydrins dominate in mono- or bis-unsaturated phosphatidylcholines. No formation of these products was detected in the absence of one of the components of the MPO-H(2)O(2)-Cl(-) system or in the presence of MPO inhibitors (sodium azide) or scavengers of hypochlorous acid (taurine, methionine). Thus, hypochlorous acid formed by the MPO-H(2)O(2)-Cl(-) system is responsible for the observed modification in unsaturated phosphatidylcholines. In the presence of the complete MPO system, lyso-products and chlorohydrins were only formed at pH values lower than pH 6.0 with an optimum at pH 4.3. In contrast, the reagent hypochlorous acid caused the formation of these products even at neutral pH values, indicating a clear dependence of the yield of products on the presence of undissociated HOCl. We conclude that the formation of lysophospholipids and chlorohydrins from unsaturated phosphatidylcholines by myeloperoxidase can be relevant in vivo under acute inflammatory conditions.