BLOCKADE OF C5A AND C5B-9 GENERATION INHIBITS LEUKOCYTE AND PLATELET ACTIVATION DURING EXTRACORPOREAL-CIRCULATION

Complement activation contributes to the systemic inflammatory response induced by cardiopulmonary bypass, At the cellular level, cardiopulmonary bypass activates leukocytes and platelets; however the contribution of early (C3a) versus late (C5a, soluble C5b-9) complement components to this activation is unclear, We used a model of simulated extracorporeal circulation that activates complement (C3a, C5a, and C5b-9 formation), platelets (increased percentages of P-selectin-positive platelets and leukocyte-platelet conjugates), and neutrophils (upregulated CD11b expression), To specifically target complement activation in this model, we added a blocking mAb directed at the human C5 complement component and assessed its effect on complement acid cellular activation, Compared with a control mAb, the anti-human C5 mAb profoundly inhibited C5a and soluble C5b-9 generation and serum complement hemolytic activity but had no effect on C3a generation, Additionally, the anti-human C5 mAb significantly inhibited neutrophil CD11b upregulation and abolished the increase in P-selectin-positive pIatelets and leukocyte-platelet conjugate formation compared to experiments performed with the control mAb, This suggests that the terminal components C5a and C5b-9, but not C3a, directly contribute to platelet and neutrophil activation during extracorporeal circulation, Furthermore, these data identify the C5 component as a site for therapeutic intervention in cardiopulmonary bypass.