KILLING OF RAT GLIAL-CELLS BY COMPLEMENT - DEFICIENCY OF THE RAT ANALOG OF CD59 IS THE CAUSE OF OLIGODENDROCYTE SUSCEPTIBILITY TO LYSIS

In an effort to understand the mechanisms of complement-mediated injur y of the myelin/oligodendrocyte complex in demyelinating disease, we h ave examined the lytic susceptibility of rat glial cells in culture. I t is known that rat oligodendrocytes are extremely sensitive to the ly tic action of autologous complement, whereas other cells in the same c ulture system, including type II astrocytes which derive from the same progenitor cell, are relatively insensitive. Here we demonstrate that the complement sensitivity of oligodendrocytes is associated with a l ack of expression of a complement-regulatory protein, the rat homologu e of human CD59, and that complement resistance can be restored by the incorporation of purified rat CD59 into the cell membrane. Furthermor e, neutralisation of rat CD59 on complement-resistant astrocytes rende rs them susceptible to lysis. Immature oligodendrocytes were resistant to complement attack yet did not express CD59, suggesting that a comp lement-activating factor appears on the membrane during oligodendrocyt e maturation.