Document Detail


Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis.
MedLine Citation:
PMID:  20424189     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Ioannis Kourtzelis; Maciej M Markiewski; Michael Doumas; Stavros Rafail; Konstantinos Kambas; Ioannis Mitroulis; Stelios Panagoutsos; Ploumis Passadakis; Vasilios Vargemezis; Paola Magotti; Hongchang Qu; Tom Eirik Mollnes; Konstantinos Ritis; John D Lambris
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-04-27
Journal Detail:
Title:  Blood     Volume:  116     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-30     Completed Date:  2010-08-30     Revised Date:  2012-09-18    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  631-9     Citation Subset:  AIM; IM    
Affiliation:
First Department of Internal Medicine Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
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MeSH Terms
Descriptor/Qualifier:
Aged
Anaphylatoxins / pharmacology,  physiology
Blood Coagulation / drug effects
Cells, Cultured
Complement Activation / drug effects
Complement C5a / metabolism,  pharmacology,  physiology*
Female
Granulocyte Colony-Stimulating Factor / metabolism
Humans
Kidney Failure, Chronic / blood,  complications,  metabolism,  therapy
Leukocytes / drug effects,  metabolism,  pathology
Male
Middle Aged
Receptor, Anaphylatoxin C5a / metabolism
Renal Dialysis / adverse effects*
Thromboplastin / metabolism
Thrombosis / etiology*
Time Factors
Grant Support
ID/Acronym/Agency:
AI068730/AI/NIAID NIH HHS; EB003968/EB/NIBIB NIH HHS; GM062134/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anaphylatoxins; 0/Receptor, Anaphylatoxin C5a; 143011-72-7/Granulocyte Colony-Stimulating Factor; 80295-54-1/Complement C5a; 9035-58-9/Thromboplastin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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