Complement activation by isolated myelin: activation of the classical pathway in the absence of myelin-specific antibodies.

Abstract

Many pathological conditions of the CNS involve damage to and removal of myelin membrane. Very little is known about initiation of this membrane damage and the mechanisms of disposal of the damaged tissue. The interaction between complement (the components of complement are designated C1, C2, C3, etc.) and myelin membranes and the possible role of complement in amplifying myelin damage and in the disposal of damaged myelin in vivo is important because activation of complement generates both membrane-attck complexes and opsonin(s). Isolated rat or human myelin consumes C in the absence of specific antibodies. Activation of C was demonstrated by showing C3 cleavage in fresh serum incubated with myelin. Incubation of CNS myelin with C2-deficient serum produced no C5 consumption and only minor factor B conversion, thus excluding the alternative pathway of activation. Involvement of the classical pathway was shown directly by the C1 fixation and transfer assay. Myelin incubated with C2-deficient serum or with purified C1 and then washed contained C1 activity that could lyse sheep erythrocytes sensitized with anti-Forssman IgM antibody and carrying C4, together with C2 and C3-C9. Membranes in brain tissues other than myelin (heavy membrane fraction obtained on sucrose density gradient centrifugation) were unable to activate C1.