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This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/F515    most recent 00527.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Crowley, S. D. Articles by Coffman, T. M. Search for Related Content PubMed PubMed Citation Articles by Crowley, S. D. Articles by Coffman, T. M.

Stimulation of lymphocyte responses by angiotensin II promotes kidney injury in hypertension

¹Division of Nephrology, Departments of Medicine and ²Pathology, Duke University Medical Center and Durham Veterans Affairs Medical Center, Durham; ³Department of Pathology, University of Miami, Miami, Florida; ⁴Department of Pathology, University of North Carolina, Chapel Hill, North Carolina; and ⁵Unit 689, Cardiovascular Research Center Lariboisiere, Institut National de la Santé et de la Recherche Médicale, Paris, France

Submitted 9 November 2007 ; accepted in final form 18 May 2008

Activation of the renin-angiotensin system contributes to the progression of chronic kidney disease. Based on the known cellular effects of ANG II to promote inflammation, we posited that stimulation of lymphocyte responses by ANG II might contribute to the pathogenesis of hypertensive kidney injury. We therefore examined the effects of the immunosuppressive agent mycophenolate mofetil (MMF) on the course of hypertension and kidney disease induced by chronic infusion of ANG II in 129/SvEv mice. Although it had no effect on the severity of hypertension or cardiac hypertrophy, treatment with MMF significantly reduced albuminuria and ameliorated kidney injury, decreasing glomerulosclerosis and reducing lymphocyte infiltration into the renal interstitium. Attenuation of renal pathology with MMF was associated with reduced expression of mRNAs for the proinflammatory cytokines interferon- and tumor necrosis factor- and the profibrotic cytokine transforming growth factor-β. As infiltration of the kidney by T lymphocytes was a prominent feature of ANG II-dependent renal injury, we carried out experiments examining the effects of ANG II on lymphocytes in vitro. We find that exposure of splenic lymphocytes to ANG II causes prominent rearrangements of the actin cytoskeleton. These actions require the activity of Rho kinase. Thus, ANG II exaggerates hypertensive kidney injury by stimulating lymphocyte responses. These proinflammatory actions of ANG II seem to have a proclivity for inducing kidney injury while having negligible actions in the pathogenesis of cardiac hypertrophy.

inflammation; kidney diseases; T lymphocytes

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