THE COMPLEMENT MEMBRANE ATTACK COMPLEX AND THE BYSTANDER EFFECT IN CEREBRAL VASOSPASM

Activation of complement results in formation of membrane attack compl exes (MACs) that can insert themselves either into cells that initiate complement activation or into nearby (''innocent bystander'') cells. The MACs form large-conductance, nonspecific ion channels that can cau se lytic or sublytic cell damage. The authors used a highly sensitive patch clamp technique to assess the contribution of the bystander effe ct to the pathophysiology of cerebral vasospasm. They compared the eff ect of complement activation by autologous aged versus fresh erythrocy tes on the membrane conductance of freshly isolated rat cerebral arter y smooth-muscle cells. In the presence of autologous serum aged, but n ot fresh, erythrocytes caused a large increase in membrane conductance , an effect that was prevented by heat-inactivating the serum. Ethylen eglycol tetraacetic acid in the presence of Mg++ attenuated the effect , indicating that complement activation was taking place via the class ic pathway. The effect was reproduced by zymosan-activated autologous serum, suggesting that such changes in conductance could result from i nsertion of MACs secondary to a bystander effect. Both C8- and C9-depl eted heterologous sera produced minimal effects that were converted to full effect by addition of the missing complement component. Superoxi de dismutase plus catalase did not attenuate the conductance changes p roduced by autologous serum plus aged erythrocytes. Autologous serum p lus aged erythrocyte membrane ghosts that were free of lysate caused a typical increase in conductance. This study demonstrates that complem ent activation by aged erythrocytes can result in MAC insertion into i nnocent bystander smooth-muscle cell membranes and chat this mechanism , heretofore undescribed, may contribute to development of vasospasm a fter subarachnoid hemorrhage.