Killing of rat glial cells by complement: deficiency of the rat analogue of CD59 is the cause of oligodendrocyte susceptibility to lysis.

In an effort to understand the mechanisms of complement-mediated injury of the myelin/oligodendrocyte complex in demyelinating disease, we have examined the lytic susceptibility of rat glial cells in culture. It is known that rat oligodendrocytes are extremely sensitive to the lytic action of autologous complement, whereas other cells in the same culture 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 lack of expression of a complement-regulatory protein, the rat homologue of human CD59, and that complement resistance can be restored by the incorporation of purified rat CD59 into the cell membrane. Furthermore, neutralisation of rat CD59 on complement-resistant astrocytes renders them susceptible to lysis. Immature oligodendrocytes were resistant to complement attack yet did not express CD59, suggesting that a complement-activating factor appears on the membrane during oligodendrocyte maturation.