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NDT Advance Access published online on May 29, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn308
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Bacterial DNA and endothelial damage in haemodialysis patients

Ana Merino, Sonia Nogueras, Tania García-Maceira, Mariano Rodríguez, Alejandro Martin-Malo, Rafael Ramirez, Julia Carracedo* and Pedro Aljama*

Unidad de Investigación, Servicio de Nefrología, Hospital Universitario Reina Sofía, Córdoba 14004, Spain

Correspondence and offprint requests to: Julia Carracedo, Unidad de Investigación, Hospital Universitario Reina Sofía, Avda Menendez Pidal S/N, Córdoba 14004, Spain. Tel: +34-957-010452; Fax: +34-957-010452; E-mail: julia.carracedo.exts{at}juntadeandalucia.es



  Abstract

Background. An increased percentage of CD14+CD16+ activated monocytes have been reported in peripheral blood from haemodialysis patients. The aim of this study is to investigate if a mild stimulus such as bacterial DNA (CpG-ODNs) contamination may induce an inflammatory response in CD14+CD16+ monocytes from haemodialysis patients and to value the biological consequences of this inflammatory response on endothelial cell damage.

Methods. Circulating mononuclear cells from 20 haemodialysis patients and 15 healthy subjects were studied. CD14+CD16+ and the toll-like receptor 9 (TLR-9) expression were assessed by flow cytometry. Cell culture inserts were used to evaluate the effect of CD14+CD16+ and CpG-ODNs on endothelial cell apoptosis (measured by Tunnel). Intracellular cytokines were measured by Cytometric methods. NF-{kappa}B, p38 MAPK, c-Jun PI3K and MEK1/2 activity were modified by specific peptides.

Results. At baseline, CD14+CD16+ have an increased expression of cytoquines and TLR-9. CpG-ODNs caused the production and release of cytoquines in CD14+CD16+, but not in CD14++ monocytes. This inflammatory response was mediated by intracellular signalling dependent on NF-{kappa}B, p38 MARK or c-Jun PI3K but not by MEK1/2 activation. The results of the present study also demonstrate that the inflammatory response induced by the stimulation of CD14+CD16+ by CpG DNA resulted in endothelial cell apoptosis.

Conclusions. The results of the present study demonstrate that in haemodialysis patients there is a subpopulation of pre-activated monocytes that can be stimulated by contaminant bacterial DNA. These activated cells produce and release inflammatory factors that may cause endothelial injury.

Keywords: bacterial DNA; endothelial damage; haemodialysis; inflammation; monocytes

* Both authors are considered co-directors of this study.

Received for publication: 15. 1.08
Accepted in revised form: 7. 5.08


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