| Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis. | |
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MedLine Citation:
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PMID: 20424189 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-04-27 |
Journal Detail:
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Title: Blood Volume: 116 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-30 Completed Date: 2010-08-30 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 631-9 Citation Subset: AIM; IM |
Affiliation:
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First Department of Internal Medicine Medical School, Democritus University of Thrace, Alexandroupolis, Greece. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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AI068730/AI/NIAID NIH HHS; EB003968/EB/NIBIB NIH HHS; GM062134/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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