Advances in Clinical and Experimental Medicine
2015, vol. 24, nr 2, March-April, p. 257–266
doi: 10.17219/acem/40463
Publication type: original article
Language: English
Download citation:
Differentiation of Monocyte Derived Dendritic Cells in End Stage Renal Disease is Skewed Towards Accelerated Maturation
1 Medical Department II, Johannes-Gutenberg University, Mainz, Germany
2 University Hospital of the Johannes Gutenberg University Mainz, Germany
3 Department of Internal Medicine-Nephrology, Vivantes Klinikum im Friedrichshain, Berlin, Germany
4 Medical Department II, Martin-Luther University, Halle-Wittenberg, Germany
5 Department of Transplant and Infection Immunology, Institute of Virology, Saarland University, Homburg/Saar, Germany
6 Department of Internal Medicine IV, Saarland University, Homburg/Saar, Germany
Abstract
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.
Objectives. 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.
Material and 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).
Conclusion. 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.
Key words
dendritic cells, hemodialysis, monocytes, end stage renal disease.
References (32)
- Collins AJ, Foley RN, Herzog C, Chavers BM, Gilbertson D, Ishani A: Excerpts from the US Renal Data System 2009 Annual Data Report. Am J Kidney Dis 2010, 55, Suppl 1, S1–420, 6–7.
- Girndt M, Sester U, Sester M, Kaul H, Köhler H: Impaired cellular immune function in patients with end-stage renal failure. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association – European Renal Association 1999, 14, 2807–2810.
- Köhler H, Arnold W, Renschin G, Dormeyer HH, Meyer zum Büschenfelde KH: Active hepatitis B vaccination of dialysis patients and medical staff. Kidney Int 1984, 25, 124–128.
- Girndt M, Köhler H, Schiedhelm-Weick E, Schlaak JF, Meyer zum Büschenfelde KH, Fleischer B: Production of interleukin-6, tumor necrosis factor alpha and interleukin-10 in vitro correlates with the clinical immune defect in chronic hemodialysis patients. Kidney Int 1995, 47, 559–565.
- Kreft B, Klouche M, Kreft R, Kirchner H, Sack K: Low efficiency of active immunization against diphtheria in chronic hemodialysis patients. Kidney Int 1997, Jul, 52, 212–216.
- Dumann H, Meuer S, Meyer zum Büschenfelde KH, Köhler H: Hepatitis B vaccination and interleukin 2 receptor expression in chronic renal failure. Kidney Int 1990, 38, 1164–1168.
- Girndt M, Köhler H, Schiedhelm Weick E, Meyer zum Büschenfelde KH, Fleischer B: T cell activation defect in hemodialysis patients: evidence for a role of the B7/CD28 pathway. Kidney Int 1993, 44, 359–365.
- Meuer SC, Hauer M, Kurz P, Meyer zum Büschenfelde KH, Köhler H: Selective blockade of the antigen-receptor-mediated pathway of T cell activation in patients with impaired primary immune responses. J Clin Invest 1987, 80, 743–749.
- Girndt M, Sester M, Sester U, Kaul H, Kohler H: Defective expression of B7-2 (CD86) on monocytes of dialysis patients correlates to the uremia-associated immune defect. 2001 2001/04//print, 59, 1382–1389.
- Belge KU, Dayyani F, Horelt A, Siedlar M, Frankenberger M, Frankenberger B: The Proinflammatory CD14+CD16+DR++ Monocytes Are a Major Source of TNF. J Immunol 2002, April 1, 2002, 168, 3536–3542.
- Durieux JJ, Vita N, Popescu O, Guette F, Calzada-Wack J, Munker R: The two soluble forms of the lipopolysaccharide receptor, CD14: characterization and release by normal human monocytes. Eur J Immunol 1994, 24, 2006–2012.
- Acunta P, Weiss L, Haeffner-Cavaillon N: CD14+CD16++ cells derived in vitro from peripheral blood monocytes exhibit phenotypic and functional dendritic cell-like characteristics. Eur J Immunol 2000, 30, 1872–1883.
- Randolph GJ, Sanchez-Schmitz G, Liebman RM, Schakel K: The CD16+ (Fc{gamma}RIII+) Subset of Human Monocytes Preferentially Becomes Migratory Dendritic Cells in a Model Tissue Setting. J Exp Med 2002, 196, 517–527.
- Steinman RM, Cohn ZA: Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 1973, 137, 1142–1462.
- Strunk D, Rappersberger K, Egger C, Strobl H, Kromer E, Maurer D: Generation of human dendritic cells/ Langerhans cells from circulating CD34+ hematopoietic progenitor cells. Blood 1996, 87, 1292–1302.
- Zhou LJ, Tedder TF: CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. Proc Natl Acad Sci 1996, 93, 2588–2592.
- Lotze MT, Thomson AW: Dendritic cells: biology and clinical applications. Academic Press, San Diego 2001, 2nd ed.
- Daugirdas JT, Ing TS: Handbook of dialysis. Little, Brown and Co, Boston–New York 1994, 2nd ed.
- Association for the Advancement of Medical Instrumentation, AAMI. American National Standards for Hemodialysis Systems. Arlington, VA: Arlington Press, 2009.
- Romani N, Reider D, Heuer M, Ebner S, Kampgen E, Eibl B: Generation of mature dendritic cells from human blood: an improved method with special regard to clicical application. J Immunol Methods 1996, 196, 137–151.
- Herbst B, Köhler G, Mackensen A, Veelken H, Mertelsmann R, Lindemann A: CD34+ peripheral blood progenitor cell and monocyte derived dendritic cells: a comparative analysis. Brit J Haematol 1997, 99, 490–499.
- Collins AJ, Foley RN, Herzog C, Chavers B, Gilbertson D, Ishani A: US Renal Data System Annual Data Report. Am J Kidney Dis 2010, 57, Suppl 1, A8, e1-526.
- Stenvinkel P, Ketteler M, Johnson RJ, Lindholm B, Pecoits-Filho R, Riella M: IL-10, IL-6, and TNF-[alpha]: Central factors in the altered cytokine network of uremia – The good, the bad, and the ugly. 2005/04//print, 67, 1216–1233.
- Schlitt A, Heine G, Blankenberg S, Dopheide JF, Lackner KJ, Iz M: CD14+CD16+ Monocytes are a Risk factor for Coronary Artery Disease and related to Serum TNF-a-levels. Thromb Haemost 2004, 92, 419–424.
- Dopheide JF, Sester U, Schlitt A, Horstick G, Rupprecht HJ, Münzel T: Monocyte-derived dendritic cells of patients with coronary artery disease show an increased expression of costimulatory molecules CD40, CD80 and CD86 in vitro. Coron Artery Dis 2007, 18, 523–531.
- Sester U, Sester M, Heine G, Kaul H, Girndt M, Köhler H: Strong depletion of CD14+CD16+ monocytes during hemodialysis treatment. Nephro Dial Transplantat 2001, 16, 1402–1408.
- Lim WH, Kireta S, Thomson AW, Russ GR, Coates PT: Renal transplantation reverses functional deficiencies in circulating dendritic cell subsets in chronic renal failure patients. Transplantation 2006, 81, 160–168.
- Lim WH, Kireta S, Leedham E, Russ GR, Coates PT: Uremia impairs monocyte and monocyte-derived dendritic cell function in hemodialysis patients. 2007 2007/08/29/online.
- Lim WH, Kireta S, Russ GR, Coates PT: Uremia impairs blood dendritic cell function in hemodialysis patients. 2007/03/21/online, 71, 1122–1131.
- Sester U, Sester M, Hauk M, Kaul H, Kohler H, Girndt M: T-cell activation follows Th1 rather than Th2 pattern in haemodialysis patients. 10.1093/ndt/15.8.1217. Nephrol Dial Transplant 2000, 15, 1217–1223.
- Puig-Kroger A, Pello OM, Selgas R, Criado G, Bajo MA, Sanchez-Tomero JA: Peritoneal dialysis solutions inhibit the differentiation and maturation of human monocyte-derived dendritic cells: effect of lactate and glucosedegradation products. J Leukoc Biol 2003, 73, 482–492.
- Agrawal S, Gollapudi P, Elahimehr R, Pahl MV, Vaziri ND: Effects of end-stage renal disease and haemodialysis on dendritic cell subsets and basal and LPS-stimulated cytokine production. Nephrol Dial Transplant 2010, 25, 737–746.