Human alternative complement pathway-mediated lysis of rabbit erythrocytes is enhanced by natural anti-Galalpha1-3Gal antibodies.

Human serum is effective at lysing unsensitized rabbit erythrocytes due to activation of the alternative complement pathway. Hemolysis is known to be enhanced by the addition of human IgG. We demonstrate that the enhancement of alternative pathway-mediated rabbit E lysis by human Ig is due to natural Abs specific for galactosyl (Gal)alpha1-3Gal. Depletion of normal human serum (NHS) of anti-Galalpha1-3Gal Abs removes almost all hemolytic activity from NHS, and activity can be restored by repletion with anti-Galalpha1-3Gal affinity-purified Abs. Factor B-depleted serum (inactive alternative pathway) did not lyse rabbit erythrocytes. Although C2-depleted serum was fully hemolytic, activity was removed by depletion of anti-Galalpha1-3Gal Abs. Of the total anti-Galalpha1-3Gal Abs affinity isolated from NHS, about one-third were IgM and two-thirds were IgG. Both anti-Galalpha1-3Gal IgG and IgM enhanced alternative pathway-mediated erythrocyte lysis.