title: Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis.
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.
authors.affiliation: First Department of Internal Medicine Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kourtzelis
authors.forename: Maciej M
authors.initials: MM
authors.lastname: Markiewski
authors.forename: Michael
authors.initials: M
authors.lastname: Doumas
authors.forename: Stavros
authors.initials: S
authors.lastname: Rafail
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kambas
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mitroulis
authors.forename: Stelios
authors.initials: S
authors.lastname: Panagoutsos
authors.forename: Ploumis
authors.initials: P
authors.lastname: Passadakis
authors.forename: Vasilios
authors.initials: V
authors.lastname: Vargemezis
authors.forename: Paola
authors.initials: P
authors.lastname: Magotti
authors.forename: Hongchang
authors.initials: H
authors.lastname: Qu
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Ritis
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
mesh_terms: 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
chemical_list: D000706:Anaphylatoxins; D044087:Receptor, Anaphylatoxin C5a; D016179:Granulocyte Colony-Stimulating Factor; D015936:Complement C5a; D013925:Thromboplastin