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NDT Advance Access originally published online on April 1, 2009
Nephrology Dialysis Transplantation 2009 24(9):2838-2846; doi:10.1093/ndt/gfp142
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© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


The HSP72 stress response of monocytes from patients on haemodialysis is impaired

Stefan Reuter1, Philip Bangen1, Bayram Edemir1, Uta Hillebrand1, Hermann Pavenstädt1, Stefan Heidenreich2 and Detlef Lang1,3

1 Department of Medicine D, University of Münster, Münster 2 KfH Dialysis Center, Aachen 3 Dialysis Center, Nordhorn, Germany

Correspondence and offprint requests to: Stefan Reuter; E-mail: sreuter{at}uni-muenster.de



  Abstract

Background. Induction of heat shock proteins (HSP), i.e. of the major family member HSP70, is an important cytoprotective-resistance mechanism for monocytes/ macrophages (Mphi). Patients on haemodialysis present with a high infectious morbidity and enhanced carcinoma incidence. Renal insufficiency-related alteration of microbicidal and tumoricidal functions of Mphi, major effectors of the immune system, might promote these diseases.

Methods. Freshly isolated Mphi from Sprague–Dawley rats 2 weeks after 5/6-nephrectomy and from patients on intermittent haemodialysis (IHD) were stimulated by heat shock (HS) and compared to stimulated Mphi of control rats or healthy volunteers (CTR). Expression of HSP72 (inducible HSP70) was assessed by RT-PCR, and/or flow cytometry. Apoptosis of Mphi was detected by flow cytometry (CD14/annexin V-labelling).

Results. In rat Mphi, baseline HSP72 expression was similar in both groups, but its induction was significantly impaired in renal insufficiency (214 ± 68% less HSP70-mRNA versus CTR, n = 6). In patients, HSF-1-mRNA and HSP72-mRNA/protein response to HS was significantly lower, but not affected by dialysis session itself. In parallel, apoptosis of Mphi of patients was enhanced (+83 ± 29% constitutive apoptotic Mphi versus CTR, n = 8), and HS-dependent protection from apoptosis with and without serum depletion (48 h depletion: HS, +275 ± 37% apoptotic Mphi versus CTR, n = 6; full medium: +166 ± 62% versus CTR, n = 8, P < 0.05) was inferior.

Conclusions. Impaired HSP72 stress response of Mphi in patients on haemodialysis might contribute to the observed immune dysfunction and, therefore, to the increased susceptibility to infection and malignancy. Stress impairment is not restricted to uraemia but is already present in a rat model of chronic kidney disease.

Keywords: apoptosis; haemodialysis; HSP72; human monocytes

Received for publication: 6.10.08
Accepted in revised form: 22. 1.09


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