Inhibition of the classical pathway of complement activation by blocking C1q with gipoxenum

Abstract

Uncontrolled activation of the complement system (CS) is one of the pathogenetic mechanisms involved in various chronic diseases of immune complexes and acute conditions such as acute myocardial intarction and hyperacute graft rejection. In the present work we studied mechanism of action o f a specific inhibitor of the classical complement pathway, not affecting CS antimicrobial function associated with alternative and lectin pathways. Hypoxenum is a drug with antioxidant and anti-hypoxic activity which binds C1q subcomponent in soiution and in immobilized state and inhibits C1q hemolytic activity (IC50=1,7x10-8 M). Hypoxenum binding to C1q included in C1 component involves the collagen-like moiety, which leads to dissociation of the complex either in solution or in immobilized state (IC50=8,9x10-9M). Hypoxenum-C1 interaction does not cause CS activation.