Selective blockade of membrane attack complex formation during simulated extracorporeal circulation inhibits platelet but not leukocyte activation
| Autor: | Brian R. Smith, Jayne B. Tracey, M. Smith, Jane C. K. Fitch, Lan Li, Christine S. Rinder, Henry M. Rinder, Scott A. Rollins |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Blood Platelets
Pulmonary and Respiratory Medicine Extracorporeal Circulation Neutrophils Macrophage-1 Antigen Enzyme-Linked Immunosorbent Assay chemical and pharmacologic phenomena Complement Membrane Attack Complex 030204 cardiovascular system & hematology Pharmacology Neutrophil Activation Extracorporeal law.invention Leukocyte Count 03 medical and health sciences 0302 clinical medicine Reference Values law Cardiopulmonary bypass Humans Medicine Platelet Platelet activation Complement Activation 030304 developmental biology 0303 health sciences biology Platelet Count business.industry Extracorporeal circulation Antibodies Monoclonal Flow Cytometry Platelet Activation Complement C8 Complement system P-Selectin Neutrophil elastase Immunology Complement C3a biology.protein Surgery Leukocyte Elastase Cardiology and Cardiovascular Medicine Complement membrane attack complex business |
| Zdroj: | The Journal of Thoracic and Cardiovascular Surgery. 118:460-466 |
| ISSN: | 0022-5223 |
| DOI: | 10.1016/s0022-5223(99)70183-2 |
| Popis: | 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, we blocked C5b-9 formation during extracorporeal recirculation of whole blood to assess whether the membrane attack complex was responsible for both platelet and leukocyte activation. Methods: In a simulated extracorporeal model that activates complement (C3a and sC5b-9), platelets (CD62P expression, leukocyte-platelet conjugate formation), and leukocytes (increased CD11b expression and neutrophil elastase), we examined an anti-human C8 monoclonal antibody that inhibits C5b-9 generation for its effects on cellular activation. Results: Anti-C8 significantly inhibited sC5b-9 formation but did not block C3a generation. Anti-C8 also significantly inhibited the increase in platelet CD62P and monocyte-platelet conjugate formation seen with control circulation. Moreover, compared with control circulation, in which the number of circulating platelets fell by 45%, addition of anti-C8 completely preserved platelet counts. In contrast to blockade of both C5a and sC5b-9 during simulated extracorporeal circulation, neutrophil activation was not inhibited by anti-C8. However, circulating neutrophil and monocyte counts were preserved by addition of anti-C8 to the extracorporeal circuit. Conclusions: The membrane attack complex, C5b-9, is the major complement determinant of platelet activation during extracorporeal circulation, whereas C5b-9 blockade 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. (J Thorac Cardiovasc Surg 1999;118:460-6) |
| Databáze: | OpenAIRE |
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