Myeloperoxidase (MPO), which is released from cytoplasmic granules of activated phagocytes by a degranulation process, reacts with H(2)O(2) (generated during the oxidative burst) and
chloride ions to generate
hypochlorous acid/
hypochlorite (HOCl/OCl(-)). HOCl, a strong
oxidant, in turn reacts with
proteins to form HOCl-modified
proteins. The presence of these cytotoxic
chloramines during inflammatory conditions, eg,
atherosclerosis and glomerular and tubulointerstitial injury, suggested that
chloramines are powerful
oxidants that can have profound
biologic effects. In the present study, immunoreactive MPO was identified in fetal membranes and the basal plate and in maternal and fetal blood cells of human placental tissues. Monocytes/macrophages represent the major cell source for MPO in human placental tissues. Immunohistochemical findings revealed that HOCl-modified
proteins are present in normal human term placenta but not during the first trimester of pregnancy (Weeks 7 to 12). HOCl-modified
proteins were localized in areas formed by fetally derived cells as well as maternal decidual tissues, ie, areas where fetal extravillous trophoblast cells invade the maternal tissue and stimulate the maternal immune system. HOCl-modified
proteins, products of the MPO-H(2)O(2)-chloride system in vivo, were not present intracellularly, but immunoreactivity for HOCl-modified
proteins was cell-associated and/or present in the extracellular matrix. Extravillous trophoblast cells, which may also exert phagocytic activities, showed no intracellular immunoreactivity for MPO or 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.