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Volume 66, Issue 4, Pages (October 2004)

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Presentation on theme: "Volume 66, Issue 4, Pages (October 2004)"— Presentation transcript:

1 Volume 66, Issue 4, Pages 1434-1443 (October 2004)
Selective lymphocyte inhibition by FTY720 slows the progressive course of chronic anti- thy 1 glomerulosclerosis  Harm Peters, Sebastian Martini, Yingrui Wang, Fuijo Shimizu, Hiroshi Kawachi, Stephanie Krämer, Hans-H. Neumayer  Kidney International  Volume 66, Issue 4, Pages (October 2004) DOI: /j x Copyright © 2004 International Society of Nephrology Terms and Conditions

2 Figure 1 Effects of FTY720 on proteinuria in chronic progressive anti-thy 1 glomerulosclerosis (cGS). FTY720 treatment was started 7 days after injection of anti-thy 1 antibody into uninephrectomized rats. Nondiseased animals with [one-kidney control (1-K control)] and without uninephrectomy [two-kidney control (2-K control)] received an injection with similar volumes of phosphate-buffered saline (PBS). Urine was collected for 24 hours at the indicated times, using metabolic cages. *P < 0.05 vs. chronic glomerulosclerosis. Kidney International  , DOI: ( /j x) Copyright © 2004 International Society of Nephrology Terms and Conditions

3 Figure 2 Effects of FTY720 on the total blood white (A) and lymphocyte cell counts (B) 20 weeks after induction of chronic anti-thy 1 glomerulosclerosis (cGS). FTY720 treatment was started 7 days after injection of anti-thy 1 antibody into uninephrectomized rats. Nondiseased animals without [two-kidney control (2-K control)] and with uninephrectomy [one-kidney control (1-K control)] received a phosphate-buffered saline (PBS) injection. Blood white cell analyses were performed by a standard automated fluorescent flow cytometry technology. ***P < vs. chronic glomerulosclerosis. Kidney International  , DOI: ( /j x) Copyright © 2004 International Society of Nephrology Terms and Conditions

4 Figure 3 Effects of FTY720 on the histologic picture 20 weeks after induction of chronic anti-thy 1 glomerulosclerosis (cGS). FTY720 treatment was started 7 days after injection of anti-thy 1 antibody into uninephrectomized rats. Shown are characteristic periodic acid-Schiff (PAS)-stained renal sections from (A) a nondiseased animal without [two-kidney control (2-K control)] and (B) with uninephrectomy [one-kidney control (1-K control)] and an animal with anti-thy 1–induced chronic progressive renal fibrosis (C) without and (D) with FTY720 treatment (magnification ×200). Kidney International  , DOI: ( /j x) Copyright © 2004 International Society of Nephrology Terms and Conditions

5 Figure 4 Effects of FTY720 on tubulointerstitial matrix accumulation (A) and cortical production of transforming growth factor-β1 (TGF-β1) (B), fibronectin (C), and plasminogen activator inhibitor (PAI-1) (D) 20 weeks after induction of chronic anti-thy 1 glomerulosclerosis (cGS). FTY720 treatment was started 7 days after injection of anti-thy 1 antibody into uninephrectomized rats. Nondiseased animals without [two-kidney control (2-K control)] and with uninephrectomy [one-kidney control (1-K control)] received a phosphate-buffered saline (PBS) injection. Matrix accumulation was scored histologically (grade 0 to 4). Matrix protein production was determined in extensively minced individual cortical tissues cultured at a density of 10 mg/mL for 48 hours. *P < 0.05 vs. chronic glomerulosclerosis. Kidney International  , DOI: ( /j x) Copyright © 2004 International Society of Nephrology Terms and Conditions

6 Figure 5 Effects of FTY720 on glomerular matrix accumulation (A) and glomerular production of transforming growth factor-β1 (TGF-β1) (B), fibronectin (C), and plasminogen activator inhibitor (PAI-1) (D) 20 weeks after induction of chronic anti-thy 1 glomerulosclerosis (cGS). Matrix accumulation was scored histologically (grade 0 to 4). Matrix protein production was determined in glomeruli harvested from individual animals and cultured at a density of 2000/mL for 48 hours. Kidney International  , DOI: ( /j x) Copyright © 2004 International Society of Nephrology Terms and Conditions

7 Figure 6 Effects of FTY720 on markers of renal function 20 weeks after induction of chronic anti-thy 1 glomerulosclerosis (cGS). Shown are plasma blood urea nitrogen (BUN) (A) and creatinine (B) levels as markers of the excretory kidney function and blood erythrocyte counts indicating the renal endocrine, erythropoetin-producing capacity. Non-diseased animals without [two kidney control (2-K control)] and with uninephrectomy [one kidney control (1-K control)] received a phosphate-buffered saline (PBS) injection. *P < 0.05 and **P < 0.01 vs. chronic glomerulosclerosis. Kidney International  , DOI: ( /j x) Copyright © 2004 International Society of Nephrology Terms and Conditions

8 Figure 7 Effects of FTY720 on tubulointerstitial cell infiltration. Shown are CD4–positive (A) and CD8–positive (B) cells indicating lymphocytes and ED-1–positive cells (C) representing macrophages 20 weeks after induction of chronic anti-thy 1 glomerulosclerosis (cGS). Nondiseased animals without [two-kidney control (2-K control)] and with uninephrectomy [one-kidney control (1-K control)] served as controls. Analysis was performed using specific murine primary antibody in conjunction with a standard APAAP technique. Data are expressed as cells per cortical section observed at ×200 magnification. *P < 0.05 and **P < 0.01 vs. chronic glomerulosclerosis. Kidney International  , DOI: ( /j x) Copyright © 2004 International Society of Nephrology Terms and Conditions

9 Figure 8 Effects of FTY720 on glomerular cell infiltration. Shown are CD4–positive (A) and CD8–positive (B) cells indicating lymphocytes and ED1–positive cells (C) representing macrophages 20 weeks after induction of chronic anti-thy 1 glomerulosclerosis (cGS). Nondiseased animals without [two-kidney control (2-K control)] and with uninephrectomy [one-kidney control (1-K control)] served as controls. Analysis was performed using specific murine primary antibody in conjunction with a standard APAAP technique. Data are expressed as cells per glomerular cross-section. **P < 0.01 vs. chronic glomerulosclerosis. Kidney International  , DOI: ( /j x) Copyright © 2004 International Society of Nephrology Terms and Conditions


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