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

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 (NH2Cl) raises with increasing NH4+ concentrations. A transchlorination from monochlorinated O-phospho-L-serine to NH4+ with the formation of NH2Cl occurs only when extraordinary high NH4+ concentrations are applied. Due to the low rate of 0.044 M-1 s(-1) for this process, a transhalogenation reaction from transient chlorinated intermediates of the serine moiety to NH4+ can be ruled out as an important process contributing to the HOCl-mediated formation of NH2Cl. A significant formation of NH2Cl 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. (C) 2010 Elsevier Inc. All rights reserved.