Volume 65, Issue 3, Pages (March 2004)

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Volume 65, Issue 3, Pages 1076-1083 (March 2004) FTY720-induced lymphocyte homing modulates post-transplant preservation/reperfusion injury Duska Dragun, Torsten Böhler, Melina Nieminen-Kelhä, Johannes Waiser, Wolfgang Schneider, Hermann Haller, Friedrich C. Luft, Klemens Budde, Hans-Hellmut Neumayer Kidney International Volume 65, Issue 3, Pages 1076-1083 (March 2004) DOI: 10.1111/j.1523-1755.2004.00478.x Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 1 FTY720, but not vehicle, induces lymphocytopenia and increases homing of lymphocytes to lymph nodes 24hours after a single-dose administration. The percentage of peripheral leukocyte subsets is shown according to granularity in vehicle (A) and FTY720 pretreated animals (B). Increased density of lymphocytes in peripheral lymph nodes after FTY720 (D) is shown, compared with vehicle treatment (C). Kidney International 2004 65, 1076-1083DOI: (10.1111/j.1523-1755.2004.00478.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 2 FTY720-treated animals are functionally protected from post-transplant ischemia/reperfusion injury (I/RI). FTY720-treated syngeneic (iso) and allogeneic (allo) recipients show significant reduction in serum creatinine concentration 24hours after transplantation compared with vehicle- (v) treated transplanted animals. *P≤ 0.05 vs. vehicle treatment. Kidney International 2004 65, 1076-1083DOI: (10.1111/j.1523-1755.2004.00478.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 3 Acute tubular necrosis score in renal isografts and allografts pretreated with FTY720 or vehicle 24hours after transplantation. *P≤ 0.05 vs. vehicle treatment. Kidney International 2004 65, 1076-1083DOI: (10.1111/j.1523-1755.2004.00478.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 4 FTY720 treatment reduces (A) intragraft neutrophil infiltration and (B) interleukin-1 (IL-1) production. *P ≤ 0.05 vs. vehicle treatment. Kidney International 2004 65, 1076-1083DOI: (10.1111/j.1523-1755.2004.00478.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 5 Effect of FTY720 on the percentage of His48-positive neutrophils in peripheral blood in recipient animals 24hours before and 24hours after transplantation. Kidney International 2004 65, 1076-1083DOI: (10.1111/j.1523-1755.2004.00478.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 6 Flow cytometry for the percentage of CD4+ lymphocytes 24hours after transplantation. Compared with vehicle (A) and (C), FTY720 depletes CD4+ lymphocytes from peripheral blood (B) and increases homing to peripheral lymph nodes (D). Kidney International 2004 65, 1076-1083DOI: (10.1111/j.1523-1755.2004.00478.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 7 Flow cytometry for the percentage of CD8+ lymphocytes 24hours after transplantation. Shown are CD8+ content in peripheral blood (A) and in lymph nodes (C) in vehicle. FTY720 depletes CD4+ lymphocytes from peripheral blood (B) and increases homing to peripheral lymph nodes (D). Kidney International 2004 65, 1076-1083DOI: (10.1111/j.1523-1755.2004.00478.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 8 Number of intragraft infiltrating endothelial-1 (ED-1)+ monocytes/macrophages (A) and major histocompatibility complex (MHC) class II–positive cells (B) in FTY720 versus vehicle- (v) pretreated isografts (iso) and allografts (allo). Kidney International 2004 65, 1076-1083DOI: (10.1111/j.1523-1755.2004.00478.x) Copyright © 2004 International Society of Nephrology Terms and Conditions

Figure 9 Expression of endothelial adhesion molecules 24hours after transplantation. Intracellular adhesion molecule-1 (ICAM-1) immunostaining in renal allograft treated with vehicle (A) or FTY720 (B). Platelet endothelial cell adhesion molecule-1 (PECAM-1) expression in renal allograft treated with vehicle (C) or FTY720 (D) is shown. Vascular cellular adhesion molecule-1 (VCAM-1) in renal allograft treated with vehicle (E) or FTY720 (F). Kidney International 2004 65, 1076-1083DOI: (10.1111/j.1523-1755.2004.00478.x) Copyright © 2004 International Society of Nephrology Terms and Conditions