BACKGROUND: Organ dysfunction followed by single-organ or even multiorgan failure due to ischemia-reperfusion injury (I/RI) is a common problem in liver and heart transplantation. Various approaches had been attempted to prevent this I/RI. One is the administration of FTY720, a synthetic structural analogue of sphingosine, which induces T-lymphocyte homing with consecutive lymphopenia. The purpose of this study was to evaluate the effect of intraoperative FTY720 administration following controlled bilateral kidney ischemia in comparison to steroid or placebo application. METHODS: Male c57BL6/J mice (n = 115; body weight 25 to 30 g) received either FTY720 (1 mg/kg body weight) or steroids or saline solution. Ischemia was applied for 30 or 60 minutes with subsequent follow-up for 48 hours. At termination all surviving animals were sacrificed. RESULTS: Following 30 minutes of ischemia, FTY720, but neither steroid nor vehicle treatment showed significant protective effects on long-term survival after controlled bilateral warm kidney ischemia. Fluorescein-activated cell sorting (FACS) analysis showed a significant T-lymphocyte depletion in peripheral blood after FTY720 treatment, which was not observed after steroid or vehicle treatment. CONCLUSION: The improved long-term survival shown in this study might be due to a protective effect of FTY720 to prevent I/RI, which may be mediated by the lymphocyte depletion shown in the FACS analysis.
BACKGROUND: Organ dysfunction followed by single-organ or even multiorgan failure due to ischemia-reperfusion injury (I/RI) is a common problem in liver and heart transplantation. Various approaches had been attempted to prevent this I/RI. One is the administration of FTY720, a synthetic structural analogue of sphingosine, which induces T-lymphocyte homing with consecutive lymphopenia. The purpose of this study was to evaluate the effect of intraoperative FTY720 administration following controlled bilateral kidney ischemia in comparison to steroid or placebo application. METHODS: Male c57BL6/J mice (n = 115; body weight 25 to 30 g) received either FTY720 (1 mg/kg body weight) or steroids or saline solution. Ischemia was applied for 30 or 60 minutes with subsequent follow-up for 48 hours. At termination all surviving animals were sacrificed. RESULTS: Following 30 minutes of ischemia, FTY720, but neither steroid nor vehicle treatment showed significant protective effects on long-term survival after controlled bilateral warm kidney ischemia. Fluorescein-activated cell sorting (FACS) analysis showed a significant T-lymphocyte depletion in peripheral blood after FTY720 treatment, which was not observed after steroid or vehicle treatment. CONCLUSION: The improved long-term survival shown in this study might be due to a protective effect of FTY720 to prevent I/RI, which may be mediated by the lymphocyte depletion shown in the FACS analysis.
Authors: Amandeep Bajwa; Sang-Kyung Jo; Hong Ye; Liping Huang; Krishna R Dondeti; Diane L Rosin; Volker H Haase; Timothy L Macdonald; Kevin R Lynch; Mark D Okusa Journal: J Am Soc Nephrol Date: 2010-03-25 Impact factor: 10.121
Authors: U Hofmann; K Hu; F Walter; N Burkard; G Ertl; J Bauersachs; O Ritter; S Frantz; A Bonz Journal: Br J Pharmacol Date: 2010-07 Impact factor: 8.739
Authors: Iryna V Samarska; Hjalmar R Bouma; Hendrik Buikema; Hubert E Mungroop; Martin C Houwertjes; Anthony R Absalom; Anne H Epema; Robert H Henning Journal: PLoS One Date: 2014-05-12 Impact factor: 3.240
Authors: Thomas V Rousselle; Canan Kuscu; Cem Kuscu; Kailo Schlegel; LiPing Huang; Maria Namwanje; James D Eason; Liza Makowski; Daniel Maluf; Valeria Mas; Amandeep Bajwa Journal: Front Immunol Date: 2020-06-23 Impact factor: 7.561