Selective blockade of membrane attack complex formation during simulated extracorporeal circulation inhibits platelet but not leukocyte activation

Objective: Complement activation is induced by cardiopulmonary bypass, and previous work found that late complement components (C5a, C5b-9) contribute to neutrophil and platelet activation during bypass. In the present study, me blocked C5b-9 formation during extracorporeal recirculation of whole bl ood to assess whether the membrane attack complex was responsible for both platelet and leukocyte activation. Methods: In a simulated extracorporeal m odel that activates complement (C3a and sC5b-9), platelets (CD62P expressio n, leukocyte-platelet conjugate formation), and leukocytes (increased CD11b expression and neutrophil elastase), we examined an anti-human C8 monoclon al antibody that inhibits C5b-9 generation for its effects on cellular acti vation. Results: Anti-GS significantly inhibited sC5b-9 formation but did n ot block C3a generation. Anti-C8 also significantly inhibited the increase in platelet CD62P and monocyte-platelet conjugate formation seen with contr ol circulation. Moreover, compared with control circulation, in which the n umber of circulating platelets fell by 45%, addition of anti-C8 completely preserved platelet counts. In contrast to blockade of both C5a and sC5b-9 d uring simulated extracorporeal circulation, neutrophil activation was not i nhibited by anti-C8 However, circulating neutrophil and monocyte counts wer e preserved by addition of anti-C8 to the extracorporeal circuit, Conclusio ns: The membrane attack complex, C5b-9, is the major complement determinant of platelet activation during extracorporeal circulation, whereas C5b-9 bl ockade has little effect on neutrophil activation. These data also suggest a role for platelet activation or C5b-9 (or both) in the loss of monocytes and neutrophils to the extracorporeal circuit.