Sepsis is caused by
infections associated with life-threatening
multiple organ failure (MOF). Septic MOF appears to be closely related to
circulatory failure due to
immunothrombosis. This process involves the production of reactive
oxygen spices (ROS) in inflammatory sites. Therefore, the detoxification of the systemic excess ROS is important for the improvement of the process in septic pathogenesis.
Histidine-rich glycoprotein (
HRG), a plasma
glycoprotein, ameliorates a septic condition through the suppression of both excess ROS production from neutrophils and
immunothrombosis.
Hydroxyl radical is known as the most important species among ROS in pathogenesis; however, the direct influence of
HRG on
hydroxyl radical formation and ROS activity is poorly understood. In this study, we showed that
HRG, in a concentration-dependent manner, efficiently inhibited the production of
hydroxyl radical induced by the Fenton's reaction through chelation of the divalent
iron.
HRG also exhibited
antioxidant activity against
peroxyl radical by oxidation of
HRG itself as a substrate; however, it did not show
superoxide dismutase and
catalase-like activities. Additionally,
HRG enhanced
glutathione peroxidase, a well-known
antioxidant enzyme, activity. These results suggest that
HRG may play a unique role in suppression of the production of
hydroxyl radicals and subsequent tissue damage at inflammatory sites. Marked reduction in plasma
HRG in
sepsis might lose such an important protective mechanism. Thus, the present study provides evidence that inhibition of ROS and ROS-production systems by
HRG may contribute to
antiseptic effects in vivo and that
HRG could be potential
therapy for ROS-related diseases.