Activation of the alternative pathway of complement in hyperacute xenograft rejection of rabbit hearts by human blood.

Isolated rabbit hearts were perfused as autoperfusing working preparations with human blood to simulate discordant hyperacute xenograft rejection. Perfusion with unmodified human blood resulted in immediate thrombotic failure of the hearts. This process was initiated by immunoglobulin M heterophile human anti-rabbit antibody, mediated by the classic pathway of complement and platelet-activating factor, and effected by platelets. Prevention of this process resulted in organ damage by another process occurring at about 20 minutes. Removal of heterophile antibody from the perfusing blood had no effect on this second event, but specific inactivation of the alternative pathway of complement prevented its generation despite normal titers of antibody and normal classic pathway activity. Studies of the deposition of components of the human complement system on the endothelium of the xenoperfused hearts confirm a role for the alternative pathway of complement in xenograft rejection in this discordant species combination.