Inhibition of carrageenan-induced paw edema by superoxide dismutase that binds to heparan sulfates on vascular endothelial cells

Abstract

The effect of heparin-binding Superoxide dismutase (HB-SOD), a fusion gene product consisting of human Cu/Zn-SOD and a C-terminal basic domain with high affinity for heparin-like proteoglycans, was examined on carrageenan-induced paw edema in mice and rats. When injected intravenously to mice just before carrageenan, HB-SOD suppressed significantly paw edema. ed 30 of HB-SOD (1000 units/kg) was markedly lower than that of SOD (bovine free Cu/Zn-SOD, 7000 units/kg). When HB-SOD was administered with heparin (500–2000 units/kg), edema was suppressed more markedly than by HB-SOD alone. In contrast, the suppressive action of SOD was decreased by heparin. HB-SOD also suppressed carrageenan paw edema in rats with an ed 30 of 2500 units/kg which was also obtained by SOD. Heparin prolonged significantly the duration of HB-SOD suppression of edema. The inhibitory effect of HB-SOD alone disappeared within 5 hr of injection, while more than 80% of the effect remained at this time when HB-SOD has been injected with 1000 units/kg of heparin. Heparin failed to enhance the anti-inflammatory effect of SOD under any of the conditions tested and heparin alone showed no suppression up to 5 hr after injection. HB-SOD might permit studies on pathophysiological events in and around vascular endothelial cells where reactive oxygen species play critical roles.