Differentiation of Monocyte Derived Dendritic Cells in End Stage Renal Disease is Skewed Towards Accelerated Maturation.
BACKGROUND
Dendritic cells (DC) play an important role in the induction of immune responses. Patients with end stage renal disease (ESRD) suffer from chronic inflammation, leading to a secondary, uremic immunodeficiency associated with alterations in monocyte subpopulations with increased proinflammatory capacities.


OBJECTIVE
The aim of this study was to examine, under isolated conditions, whether alterations in monocyte subpopulations may affect in vitro maturation of dendritic cells (DC) in patients with ESRD, thus allowing us to draw conclusions for the situation in vivo.


METHODS
Monocytes from 30 patients undergoing hemodialysis (HD) and 15 healthy volunteers were enriched from peripheral blood leukocytes, differentiated into immature DC (iDC) in medium containing IL-4 and GM-CSF, and were induced with LPS to differentiate into mature DC (mDC). Monocyte subpopulations and DC maturation stages were phenotypically characterized using flow-cytometry.


RESULTS
Although phenotypically indistinguishable, the number of both iDC and mDC that were generated from uremic monocytes was significantly higher compared to those from healthy controls (p=0.02 and p=0.03, respectively). This was associated with an increased number of CD14+ CD16+ monocytes (p=0.02) and by a higher maturation efficiency of mDC in patients (p=0.04).


CONCLUSIONS
A high percentage of CD14+ CD16+ monocytes in patients with ESRD is associated with an increased propensity to differentiate into DC. This indicates that chronic inflammation may substantiate the biased consistence of monocyte subpopulations leading to profound alteration in DC generation and maturation in ESRD.
Medical Department II, Johannes-Gutenberg University, Mainz, Germany.
Joern F
JF
Dopheide
University Hospital of the Johannes Gutenberg University Mainz, Germany.
Geraldine C
GC
Zeller
Department of Internal Medicine-Nephrology, Vivantes Klinikum im Friedrichshain, Berlin, Germany.
Martin
M
Kuhlmann
Medical Department II, Martin-Luther University, Halle-Wittenberg, Germany.
Matthias
M
Girndt
Department of Transplant and Infection Immunology, Institute of Virology, Saarland University, Homburg/Saar, Germany.
Martina
M
Sester
Department of Internal Medicine IV, Saarland University, Homburg/Saar, Germany.
Urban
U
Sester
D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000628:therapy; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D006435:Renal Dialysis; D013997:Time Factors
D015415:Biomarkers; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D017452:Receptors, IgG