Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis
- 29 July 2010
- journal article
- Published by American Society of Hematology in Blood
- Vol. 116 (4), 631-639
- https://doi.org/10.1182/blood-2010-01-264051
Abstract
Thrombosis is a common complication of end-stage renal disease, particularly in patients on hemodialysis. Although substantial progress has been made in preventing thrombotic complications in various other groups of patients, the mechanisms of thrombosis during hemodialysis require clarification. In this report, we demonstrate that complement activation triggered by hemodialysis biomaterials, and the subsequent generation of the complement anaphylatoxin C5a, results in the expression of functionally active tissue factor (TF) in peripheral blood neutrophils. Because TF is a key initiator of coagulation in vivo, we postulate that the recurring complement activation that occurs during long-term hemodialysis contributes to thrombosis in dialyzed end-stage renal disease patients. Furthermore, we found that complement contributed to the induction of granulocyte colony-stimulating factor, which has been implicated in the pathogenesis of thrombosis in patients treated with the recombinant form of this molecule. Importantly, the inhibition of complement activation attenuated the TF expression and granulocyte colony-stimulating factor induction in blood passing through a hemodialysis circuit, suggesting that the complement system could become a new therapeutic target for preventing thrombosis in patients with chronic renal failure who are maintained on hemodialysis.Keywords
This publication has 45 references indexed in Scilit:
- Can cells and biomaterials in therapeutic medicine be shielded from innate immune recognition?Trends in Immunology, 2009
- Recent developments in low molecular weight complement inhibitorsMolecular Immunology, 2009
- Inflammation in chronic kidney disease: role in the progression of renal and cardiovascular diseasePediatric Nephrology, 2009
- Levels of microparticle tissue factor activity correlate with coagulation activation in endotoxemic miceJournal of Thrombosis and Haemostasis, 2009
- Interleukin-17 and Interferon-γ Are Produced Concomitantly by Human Coronary Artery–Infiltrating T Cells and Act Synergistically on Vascular Smooth Muscle CellsCirculation, 2009
- Complement-targeted therapeuticsNature Biotechnology, 2007
- Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody–induced fetal injuryBlood, 2007
- The Role of Complement in Inflammatory Diseases From Behind the Scenes into the SpotlightThe American Journal of Pathology, 2007
- Adverse Effects on Hemostatic Function of Drugs Used in Hematologic MalignanciesSeminars in Thrombosis and Hemostasis, 2007
- Complement and Leukocyte-Mediated Pulmonary Dysfunction in HemodialysisNew England Journal of Medicine, 1977