Interaction of hypochlorous acid and myeloperoxidase with phosphatidylserine in the presence of ammonium ions

摘要

The close association of the heme enzyme myeloperoxidase to phosphatidylserine epitopes on the surface of non-vital polymorphonuclear leukocytes (PMNs) and other apoptotic cells at inflammatory sites favours modifications of this phospholipid by myeloperoxidase products. As detected by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, ammonium ions inhibit in a concentration-dependent manner the hypochlorous acid-mediated formation of aldehyde and nitrile products from 1,2-dipalmitoyl-sn-glycero-3-phosphoserine (DPPS). Concomitantly, the formation of monochloramine (NH_2Cl) raises with increasing NH_4~+ concentrations. A transchlorination from monochlorinated O-phospho-l-serine to NH_4~+ with the formation of NH_2Cl occurs only when extraordinary high NH_4~+ concentrations are applied. Due to the low rate of 0.044M~(-1)s~(-1) for this process, a transhalogenation reaction from transient chlorinated intermediates of the serine moiety to NH_4~+ can be ruled out as an important process contributing to the HOCl-mediated formation of NH_2Cl. A significant formation of NH_2Cl by myeloperoxidase interacting with DPPS in the presence of ammonium ions takes only place at acidic pH values around 5, a scenario that may occur in phagosomes of macrophages after the uptake of apoptotic PMNs.