Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis.
Τίτλος | Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Kourtzelis, I., Markiewski M. M., Doumas M., Rafail S., Kambas K., Mitroulis I., Panagoutsos S., Passadakis P., Vargemezis V., Magotti P., Qu H., Mollnes T. Eirik, Ritis K., & Lambris J. D. |
Journal | Blood |
Volume | 116 |
Issue | 4 |
Pagination | 631-9 |
Date Published | 2010 Jul 29 |
ISSN | 1528-0020 |
Λέξεις κλειδιά | Aged, Anaphylatoxins, Blood Coagulation, Cells, Cultured, Complement Activation, Complement C5a, Female, Granulocyte Colony-Stimulating Factor, Humans, Kidney Failure, Chronic, Leukocytes, Male, Middle Aged, Receptor, Anaphylatoxin C5a, Renal Dialysis, Thromboplastin, Thrombosis, Time Factors |
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. |
DOI | 10.1182/blood-2010-01-264051 |
Alternate Journal | Blood |
PubMed ID | 20424189 |
PubMed Central ID | PMC3086498 |
Grant List | AI068730 / AI / NIAID NIH HHS / United States EB003968 / EB / NIBIB NIH HHS / United States GM062134 / GM / NIGMS NIH HHS / United States |