The complement membrane attack complex and the bystander effect in cerebral vasospasm.
Activation of complement results in formation of membrane attack complexes (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 cause lytic or sublytic cell damage. The authors used a highly sensitive patch clamp technique to assess the contribution of the bystander effect to the pathophysiology of cerebral vasospasm. They compared the effect of complement activation by autologous aged versus fresh erythrocytes on the membrane conductance of freshly isolated rat cerebral artery smooth-muscle cells. In the presence of autologous serum aged, but not fresh, erythrocytes caused a large increase in membrane conductance, an effect that was prevented by heat-inactivating the serum. Ethyleneglycol tetraacetic acid in the presence of Mg++ attenuated the effect, indicating that complement activation was taking place via the classic pathway. The effect was reproduced by zymosan-activated autologous serum, suggesting that such changes in conductance could result from insertion of MACs secondary to a bystander effect. Both C8- and C9-depleted heterologous sera produced minimal effects that were converted to full effect by addition of the missing complement component. Superoxide dismutase plus catalase did not attenuate the conductance changes produced by autologous serum plus aged erythrocytes. Autologous serum plus aged erythrocyte membrane ghosts that were free of lysate caused a typical increase in conductance. This study demonstrates that complement activation by aged erythrocytes can result in MAC insertion into innocent bystander smooth-muscle cell membranes and that this mechanism, heretofore undescribed, may contribute to development of vasospasm after subarachnoid hemorrhage.
Park
C C
CC
Department of Neurosurgery, University of Maryland School of Medicine, Baltimore 21201, USA.
Shin
M L
ML
Simard
J M
JM
D000818:Animals; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D003165:Complement System Proteins / Q000502:physiology*; D004912:Erythrocytes / Q000502:physiology*; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008564:Membrane Potentials / Q000502:physiology*; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats
D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins