Interactions between Human C5, C6, and C7 and Their Functional Significance in Complement-Dependent Cytolysis

Abstract

Abstract Two types of complexes were observed between C5, C6 and C7. In their native form these three complement proteins enter into reversible interactions which were demonstrated by zone ultracentrifugation. Interactions between C5 and C6 occurred in absence of C7 and between C5 and C7 in absence of C6. Presence of C6, however, enhanced the association of C5 and C7. Formation of a stable C5–C6 complex was effected by the complement enzyme . This complex () had a sedimentation coefficient of 12 to 14S and exhibited the ability to attach itself firmly to non-sensitized sheep erythrocytes (E) in presence of C7. activity was also generated by trypsin or plasmin, suggesting the existence of a new pathway of complement activation by non-complement enzymes beginning with C5. produced with trypsin or displayed typical ultrastructural membrane lesions and was susceptible to lysis by C8 and C9. Regardless of experimental conditions, C5, C6, and C7 were taken up by the surface of cells in equimolar quantities. The affinity between native C5, C6, and C7 displayed in free solution, and the equimolarity of the cell-bound equivalents, support the concept of a firm trimolecular assembly as the topologic base of the membrane attack mechanism of complement.