Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis.
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.
Kourtzelis
Ioannis
I
First Department of Internal Medicine Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
Markiewski
Maciej M
MM
Doumas
Michael
M
Rafail
Stavros
S
Kambas
Konstantinos
K
Mitroulis
Ioannis
I
Panagoutsos
Stelios
S
Passadakis
Ploumis
P
Vargemezis
Vasilios
V
Magotti
Paola
P
Qu
Hongchang
H
Mollnes
Tom Eirik
TE
Ritis
Konstantinos
K
Lambris
John D
JD
D000368:Aged; D000706:Anaphylatoxins / Q000494:pharmacology / Q000502:physiology; D001777:Blood Coagulation / Q000187:drug effects; D002478:Cells, Cultured; D003167:Complement Activation / Q000187:drug effects; D015936:Complement C5a / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000628:therapy; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism; D006435:Renal Dialysis / Q000009:adverse effects*; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology*; D013997:Time Factors
D000706:Anaphylatoxins; D044087:Receptor, Anaphylatoxin C5a; D016179:Granulocyte Colony-Stimulating Factor; D015936:Complement C5a; D013925:Thromboplastin