Submitted on September 7, 2008
Revised on May 29, 2009
Accepted on June 17, 2009
Role of FTY720 on M1 and M2 macrophages, lymphocytes and chemokines in 5/6 nephrectomized rats
Matthias Schaier1*, Stefanie Vorwalder1, Claudia Sommerer1, Ralf Dikow1, Friederike Hug1, Marie-Luise Gross1, Ruediger Waldherr1, and Martin Zeier2
1 University of Heidelberg
2 University Hospital Heidelberg
* To whom correspondence should be addressed. E-mail: matthias_schaier{at}med.uni-heidelberg.de.
Renal injury is accompanied by the presence of infiltrating inflammatory cells in the glomerulus and tubulointerstitium. FTY720 modifies lymphocyte migration into injured tissues by lymphocyte sequestration to secondary lymphoid organs. The purpose of this study was to examine the potential of FTY720 to influence inflammatory response in a non-immunological model of renal failure. Sham-operated and 5/6 nephrectomized Sprague Dawley rats received two different doses of FTY720 or vehicle orally for 14 weeks. Treatment with FTY720 reduced glomerular and tubulointerstitial damage in SNX rats but failed to stabilize creatinine-clearance. The increase of the chemokine receptors CCR1, CCR2 and CCR5 gene expression in kidneys of vehicle-treated SNX rats was significantly attenuated by high-dose FTY720. Treatment with high-dose FTY720 tended to normalize RANTES and MCP-1 renal gene expression. FTY720 did not only affect glomerular and tubulointerstitial lymphocytes, but also M1 and M2 phenotype macrophages were reduced. FTY720 reduced significantly key mediators of renal inflammation and fibrosis. FTY720 also decreased immunoregulation M2 macrophages which are beneficial for tissue remodelling and repair.
