The natural anticoagulant Thrombomodulin has radical scavenging activity and acts as an antioxidant C-type lectin

Abstract number: OC381

Maruyama^* I., Yamaji^* K., Kawahara^* K., Sarker^* K. P., Iino^* S., Yamakuchi^* M., Stern† D. M., Abeyama^* K.

^*School of Medicine, Kagoshima University, Japan; †School of Medicine, Medical College of Georgia, USA

Thrombomodulin (TM) is an endothelial C-type lectin which acts as a natural anticoagulant by converting thrombin from a procoagulant to an anticoagulant enzyme. Recent studies have suggested anti-inflammatory and cytoprotective properties of TM, though mechanisms underlying these findings, beyond binding thrombin and promoting formation of activated protein C, remain uncertain. Our studies have demonstrated antioxidant properties of TM. TM showed significant inhibitory activity for several cell-mediated events triggered by reactive oxygen intermediates (ROIs), including platelet aggregation, phorbol ester-induced oxidant stress, X-ray irradiation-induced activation of NF-kappa B and loss of cell viability, and hydrogen peroxide-induced cell death. These properties of TM were independent of enhanced protein C activation or carboxypeptidase R (CPR) activity. TM, but not other endothelial C-type lectins, inhibited copper-induced lipid peroxidation of LDL. Furthermore, electron spin resonance analysis revealed potent antioxidative properties of recombinant TM. Taken together, these data suggest that TM, via its antioxidant properties, may exert important cytoprotective and anti-inflammatory effects in settings of oxidant stress quite distinct from its anticoagulant activity.