Myeloperoxidase-dependent generation of hypochlorite-modified proteins in human placental tissues during normal pregnancy

Myeloperoxidase (MPO), which is released from cytoplasmic granules of activ ated phagocytes by a degranulation process, reacts with H2O2 (generated dur ing the oxidative burst) and chloride ions to generate hypochlorous acid/hy pochlorite (HOCl/OCl-). HOCl, a strong oxidant, in turn reacts with protein s to form HOCl-modified proteins. The presence of these cytotoxic chloramin es during inflammatory conditions, eg, atherosclerosis and glomerular and t ubulointerstitial injury, suggested that chloramines are powerful oxidants that can have profound biologic effects. In the present study, immunoreacti ve MPO was identified in fetal membranes and the basal plate and in materna l and fetal blood cells of human placental tissues. Monocytes/macrophages r epresent the major cell source for MPO in human placental tissues. Immunohi stochemical findings revealed that HOCl-modified proteins are present in no rmal human term placenta but not during the first trimester of pregnancy (W eeks 7 to 12). HOCl-modified proteins were localized in areas formed by fet ally derived cells as well as maternal decidual tissues, ie, areas where fe tal extravillous trophoblast cells invade the maternal tissue and stimulate the maternal immune system. HOCl-modified proteins, products of the MPO-H2 O2-chloride system in vivo, were not present intracellularly, but immunorea ctivity for HOCl-modified proteins was cell-associated and/or present in th e extracellular matrix. Extravillous trophoblast cells, which may also exer t phagocytic activities, showed no intracellular immunoreactivity for MPO o r HOCl-modified proteins. The present findings indicate that the generation of HOCl-modified proteins during normal pregnancy is a physiologic rather than a pathophysiologic process.