Complement activation after oxidative stress - Role of the lectin complement pathway

The complement system plays an important role in mediating tissue injury af ter oxidative stress. The role of mannose-binding lectin (MBL) and the lect in complement pathway (LCP) in mediating complement activation after endoth elial oxidative stress was investigated, iC3b deposition on hypoxic (24 hou rs; 1% O-2)/ reoxygenated (3 hours; 21% O-2) human endothelial cells was at tenuated by N-acetyl-D-glucosamine or D-mannose, but not L-mannose, in a do se-dependent manner. Endothelial iC3b deposition after oxidative stress was also attenuated in MBL-deficient serum. Novel, functionally inhibitory, an ti-human MBL mono-clonal antibodies attenuated MBL-dependent C3 deposition on mannan-coated plates in a dose-dependent manner. Treatment of human seru m with anti-MBL monoclonal antibodies inhibited MBL and C3 deposition after endothelial oxidative stress. Consistent with our in vitro findings, C3 an d MBL immunostaining throughout the ischemic area at risk increased during rat myocardial reperfusion in vivo. These data suggest that the LCP mediate s complement activation after tissue oxidative stress. Inhibition of MBL ma y represent a novel therapeutic strategy for ischemia/reperfusion injury an d other complement-mediated disease states.