Inhibition of the terminal stage of complement-mediated lysis (reactive lysis) by zinc and copper ions.

The effect of various metal ions, Fe++, Fe+++, Cu++, Zn++, Co++, on the terminal stage of reactive lysis (a form of complement-mediated hemolysis in which only late-acting components of complement are required) was studied. Only Cu++ and Zn++ exhibited an inhibitory effect on the lysis of EC5678 (sheep erythrocytes reacted with C56, C7 and C8) induced by C9. The mode of action of these metal ions was further explored. Both Cu++ and Zn++ inhibited the formation of hemolytically active EC56789 from EC5678 and C9. Their effect appeared to be primarily due to the inhibition of C9 binding to EC5678 through their reversible interaction with C9. Furthermore, Cu++ is shown to inactivate irreversibly the hemolytic activity of EC5678. EC5678 pretreated with Cu++ was capable of binding C9, but the resulting EC56789 was hemolytically inactive. Besides their effect on complement, both metal ions were shown to affect directly the erythrocyte membrane, since the mechanical lysis of hemolytic intermediate cells (E, EC567, EC5678) was suppressed by Cu++ and Zn++. The lysis of EC56789, a process of internal activation, was also inhibited by both Cu++ and Zn++.