Contrasting Effects of Systemic Monocyte/Macrophage and CD4+ T Cell Depletion in a Reversible Ureteral Obstruction Mouse Model of Chronic Kidney Disease

Using a reversible UUO model (rUUO), we have demonstrated that C57BL/6 mice are susceptible to development of CKD after obstruction-mediated kidney injury while BALB/c mice are resistant. We hypothesized that selective systemic depletion of subpopulations of inflammatory cells during injury or repai...

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Main Authors: Lee D. Chaves, Liby Mathew, Mohammed Shakaib, Anthony Chang, Richard J. Quigg, Tipu S. Puri
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2013/836989
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author Lee D. Chaves
Liby Mathew
Mohammed Shakaib
Anthony Chang
Richard J. Quigg
Tipu S. Puri
author_facet Lee D. Chaves
Liby Mathew
Mohammed Shakaib
Anthony Chang
Richard J. Quigg
Tipu S. Puri
author_sort Lee D. Chaves
collection DOAJ
description Using a reversible UUO model (rUUO), we have demonstrated that C57BL/6 mice are susceptible to development of CKD after obstruction-mediated kidney injury while BALB/c mice are resistant. We hypothesized that selective systemic depletion of subpopulations of inflammatory cells during injury or repair might alter the development of CKD. To investigate the impact of modification of Th-lymphocytes or macrophage responses on development of CKD after rUUO, we used an anti-CD4 antibody (GK1.5) or liposomal clodronate to systemically deplete CD4+ T cells or monocyte/macrophages, respectively, prior to and throughout the rUUO protocol. Flow cytometry and immunohistochemistry confirmed depletion of target cell populations. C57BL/6 mice treated with the GK1.5 antibody to deplete CD4+ T cells had higher BUN levels and delayed recovery from rUUO. Treatment of C57BL/6 mice with liposomal clodronate to deplete monocyte/macrophages led to a relative protection from CKD as assessed by BUN values. Our results demonstrate that modulation of the inflammatory response during injury and repair altered the susceptibility of C57BL/6 mice to development of CKD in our rUUO model.
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spelling doaj-art-d5ab2a1723714fbd8062acf8eaa702d32025-02-03T06:01:44ZengWileyClinical and Developmental Immunology1740-25221740-25302013-01-01201310.1155/2013/836989836989Contrasting Effects of Systemic Monocyte/Macrophage and CD4+ T Cell Depletion in a Reversible Ureteral Obstruction Mouse Model of Chronic Kidney DiseaseLee D. Chaves0Liby Mathew1Mohammed Shakaib2Anthony Chang3Richard J. Quigg4Tipu S. Puri5Division of Nephrology, Department of Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences, 875 Ellicott Street, Buffalo, NY 14202, USASection of Nephrology, Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USASection of Nephrology, Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USADepartment of Pathology, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USADivision of Nephrology, Department of Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences, 875 Ellicott Street, Buffalo, NY 14202, USASection of Nephrology, Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USAUsing a reversible UUO model (rUUO), we have demonstrated that C57BL/6 mice are susceptible to development of CKD after obstruction-mediated kidney injury while BALB/c mice are resistant. We hypothesized that selective systemic depletion of subpopulations of inflammatory cells during injury or repair might alter the development of CKD. To investigate the impact of modification of Th-lymphocytes or macrophage responses on development of CKD after rUUO, we used an anti-CD4 antibody (GK1.5) or liposomal clodronate to systemically deplete CD4+ T cells or monocyte/macrophages, respectively, prior to and throughout the rUUO protocol. Flow cytometry and immunohistochemistry confirmed depletion of target cell populations. C57BL/6 mice treated with the GK1.5 antibody to deplete CD4+ T cells had higher BUN levels and delayed recovery from rUUO. Treatment of C57BL/6 mice with liposomal clodronate to deplete monocyte/macrophages led to a relative protection from CKD as assessed by BUN values. Our results demonstrate that modulation of the inflammatory response during injury and repair altered the susceptibility of C57BL/6 mice to development of CKD in our rUUO model.http://dx.doi.org/10.1155/2013/836989
spellingShingle Lee D. Chaves
Liby Mathew
Mohammed Shakaib
Anthony Chang
Richard J. Quigg
Tipu S. Puri
Contrasting Effects of Systemic Monocyte/Macrophage and CD4+ T Cell Depletion in a Reversible Ureteral Obstruction Mouse Model of Chronic Kidney Disease
Clinical and Developmental Immunology
title Contrasting Effects of Systemic Monocyte/Macrophage and CD4+ T Cell Depletion in a Reversible Ureteral Obstruction Mouse Model of Chronic Kidney Disease
title_full Contrasting Effects of Systemic Monocyte/Macrophage and CD4+ T Cell Depletion in a Reversible Ureteral Obstruction Mouse Model of Chronic Kidney Disease
title_fullStr Contrasting Effects of Systemic Monocyte/Macrophage and CD4+ T Cell Depletion in a Reversible Ureteral Obstruction Mouse Model of Chronic Kidney Disease
title_full_unstemmed Contrasting Effects of Systemic Monocyte/Macrophage and CD4+ T Cell Depletion in a Reversible Ureteral Obstruction Mouse Model of Chronic Kidney Disease
title_short Contrasting Effects of Systemic Monocyte/Macrophage and CD4+ T Cell Depletion in a Reversible Ureteral Obstruction Mouse Model of Chronic Kidney Disease
title_sort contrasting effects of systemic monocyte macrophage and cd4 t cell depletion in a reversible ureteral obstruction mouse model of chronic kidney disease
url http://dx.doi.org/10.1155/2013/836989
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