A reason for the cytolytic inefficiency of murine serum

Murine serum exhibits very poor haemolytic and bactericidal activity. We report that this is due, at least in part, to the presence of a potent, naturally occurring plasma inhibitor of the terminal complement sequence. The inhibitor is a heat-stable euglobulin. It is highly effective in suppressing haemolysis following complement activation on target erythrocytes with heterologous serum. It also inhibits C3-independent reactive haemolysis of guinea-pig erythrocytes with human C5b-9. Current evidence indicates that the inhibitory factor acts at the C5b-7 stage by preventing binding of the terminal complement complex to cells undergoing complement attack. In this respect, the inhibitor differs from the previously recognized regulators of the terminal complement sequence including plasma S-protein. The inhibitor does not protect C5b-7-laden cells from the action of C8 and C9, and also does not suppress formation of haemolytically inactive SC5b-9 in the fluid phase. The action of murine inhibitory factor is not confined to the red cell, and its presence can totally abolish the bactericidal activity of human serum on a sensitive, rough E. coli K12 strain.