Related Experiment Videos
Myeloperoxidase-dependent generation of hypochlorite-modified proteins in human placental tissues during normal
1Institute of Histology and Embryology, Karl-Franzens University Graz, Graz, Austria.
Abstract:
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.
Insights
Hypochlorous acid-modified proteins, generated by myeloperoxidase (MPO) in the placenta, are present in normal pregnancy. Their presence indicates a physiological process, not a pathological one, during gestation.
Area of Science:
- Reproductive biology
- Immunology
- Biochemistry
Background:
- Myeloperoxidase (MPO) produces hypochlorous acid (HOCl), a potent oxidant.
- HOCl modifies proteins, forming cytotoxic chloramines implicated in inflammatory diseases.
- The role of MPO and HOCl-modified proteins in placental physiology is not well understood.
Purpose of the Study:
- To investigate the presence and localization of MPO and HOCl-modified proteins in human placental tissues.
- To determine if HOCl-modified proteins are associated with normal pregnancy or pathological conditions.
Main Methods:
- Immunohistochemistry was used to detect immunoreactive MPO and HOCl-modified proteins in human placental tissues from different gestational stages.
- Cellular sources of MPO and localization of HOCl-modified proteins were analyzed.
Main Results:
- Immunoreactive MPO was found in maternal/fetal blood cells and monocytes/macrophages in the placenta.
- HOCl-modified proteins were detected in normal term placenta but absent in early pregnancy (Weeks 7-12).
- These proteins were localized in areas of fetomaternal cell interaction, associated with the extracellular matrix, not intracellularly.
Conclusions:
- The generation of HOCl-modified proteins in the human placenta during normal pregnancy is a physiological process.
- This process is distinct from the pathological role of chloramines in inflammatory conditions.
- Extravillous trophoblast cells, despite potential phagocytic activity, do not show intracellular MPO or HOCl-modified proteins.