A link between active myeloperoxidase and chlorinated ceruloplasmin in blood plasma of patients with cardiovascular diseases

Abstract

Myeloperoxidase is a key factor promoting development of halogenative/oxidative stress under inflammatory conditions. Previously, we have discovered complexes including myeloperoxidase and its physiological inhibitor, ceruloplasmin in blood plasma of patients with inflammatory diseases of different etiology, e.g., atherosclerosis. Studies on regulation of myeloperoxidase activity by ceruloplasmin have shown that hypochlorous acid, a specific product of myeloperoxidase action, is likely to modify ceruloplasmin during inflammation. The present study was aimed for analysis of relationships between the myeloperoxidase activity, native, and HOCl-modified ceruloplasmin levels in blood plasma samples of the patients with cardiovascular diseases. Specific antibodies against myeloperoxidase, ceruloplasmin, and HOCl-modified ceruloplasmin were obtained and specific enzyme-linked immunosorbent assays (ELISA) were developed. A combination of highly sensitive methods of myeloperoxidase assay i.e., solid-phase adsorption of antigens with subsequent testing of either their activity, or peroxidase-labeled antibody activity allowed elaborating the highly sensitive assays for ceruloplasmin and its HOCl-modified molecules, and for myeloperoxidase (concentration, peroxidase and halogenating activity). Positive correlation was proven between the myeloperoxidase concentration and activities. HOCl-modified ceruloplasmin content also correlated with myeloperoxidase activity. The HOCl-modified ceruloplasmin was first discovered in blood plasma samples from patients with cardiovascular diseases. In view of correlation between myeloperoxidase activity and HOCl-modified ceruloplasmin content in plasma, we suggest that HOCl production is aimed for suppression of myeloperoxidase-inhibitory function of ceruloplasmin.