Low superoxide scavenging activity associated with enhanced superoxide generation by monocytes from male...

To investigate the mechanism of increased superoxide (O2-) generation by monocytes from patients with hypertriglyceridemia, superoxide scavenging activity (SSA) and O2- generation by monocytes were determined concomitantly employing an electron spin resonance/spin trapping method and 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo [1,2-a]-pyrazin-3-one (MCLA)-dependent chemiluminescence, respectively. Peripheral monocytes were separated by the adherent methods from the following four male groups: normal control, diabetes alone (DM), diabetes with hypertriglyceridemia (DM + HTG) and hypertriglyceridemia alone (HTG). Monocytes were stimulated by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) or opsonized zymosan (OZ). O2- generation by monocytes upon stimulation was enhanced in HTG and HTG + DM but not in DM as compared to that in normal controls. The mean value of SSA in monocytes was similar among the 4 groups. When the relationship was analyzed using various parameters, a significant positive relationship was found between O2- generation and the plasma triglyceride level; a significant negative correlation was found between SSA and both the O2- generation and the plasma triglyceride level. In the in vitro system, the SSA in monocytes decreased significantly after the the stimulation by either of PMA or OZ. The results indicate that the decrease of SSA in monocytes may originate from the enhanced in vivo O2- generation and is responsible for the enhanced O2- release against the stimuli in hypertriglyceridemia. These abnormal functions of monocytes may in part accelerate the development of atherosclerosis.