허혈/재관류 손상은 급성신부전의 주요 원인이며 이식된 신장의 기능지연을 유발하여 거부반응의 발생을 증가시킨다. 본 연구에서는 쥐의 허혈/재관류 손상모델에서 허혈시간에 따른 면역세포의 변화를 평가하였다. 8주령 수컷 SD rat의 좌신을 각각 30, 45, 60분간 허혈/재관류 동안에 우신을 적출 하였고, 대조군은 우신만 적출하였다. 신장기능은 0, 1, 2, 3, 5, 7일에 각각 평가하였으며, 허혈/재관류 후 1일과 7일에 신장조직을 채취하여 면역형광염색(DCs, NK cells, macrophages, B cells, CD4+ and CD8+ T cells)과 H&E 염색을 실시하였다. 허혈 시간이 증가할수록 신장기능이 감소되었으나, 신장 세뇨관괴사와 염증세포의 침윤이 증가하였다. 허혈/재관류 후 신장조직에서 DCs, NK cells, macrophages, CD4+ T cells, CD8+ T cells의 침윤 증가와 재관류 후 7일째 B cells의 침윤이 관찰되었다. 면역세포는 허혈시간 뿐 아니라 재관류 시간이 증가에 따라 뚜렷하게 관찰되었다. 이 결과는 허혈시간이 증가됨에 따라 면역반응이 증가될 수 있으며, 허혈재관류 손상이 비항원성 면역반응을 유도할 수도 있다는 것을 의미한다.
허혈/재관류 손상은 급성신부전의 주요 원인이며 이식된 신장의 기능지연을 유발하여 거부반응의 발생을 증가시킨다. 본 연구에서는 쥐의 허혈/재관류 손상모델에서 허혈시간에 따른 면역세포의 변화를 평가하였다. 8주령 수컷 SD rat의 좌신을 각각 30, 45, 60분간 허혈/재관류 동안에 우신을 적출 하였고, 대조군은 우신만 적출하였다. 신장기능은 0, 1, 2, 3, 5, 7일에 각각 평가하였으며, 허혈/재관류 후 1일과 7일에 신장조직을 채취하여 면역형광염색(DCs, NK cells, macrophages, B cells, CD4+ and CD8+ T cells)과 H&E 염색을 실시하였다. 허혈 시간이 증가할수록 신장기능이 감소되었으나, 신장 세뇨관괴사와 염증세포의 침윤이 증가하였다. 허혈/재관류 후 신장조직에서 DCs, NK cells, macrophages, CD4+ T cells, CD8+ T cells의 침윤 증가와 재관류 후 7일째 B cells의 침윤이 관찰되었다. 면역세포는 허혈시간 뿐 아니라 재관류 시간이 증가에 따라 뚜렷하게 관찰되었다. 이 결과는 허혈시간이 증가됨에 따라 면역반응이 증가될 수 있으며, 허혈재관류 손상이 비항원성 면역반응을 유도할 수도 있다는 것을 의미한다.
Ischemia/reperfusion injury(I/RI) is the major cause of acute renal failure and delayed graft function(DGF) unavoidable in renal transplantation. Enormous studies on ischemia damage playing a role in activating graft rejection factors, such as T cells or macrophages, are being reported. Present stud...
Ischemia/reperfusion injury(I/RI) is the major cause of acute renal failure and delayed graft function(DGF) unavoidable in renal transplantation. Enormous studies on ischemia damage playing a role in activating graft rejection factors, such as T cells or macrophages, are being reported. Present study was performed to determine whether ischemia time would play an important role in activating rejection-related factors or not in rat models of I/RI. Male Sprague-Dawley rats were submitted to 30, 45, and 60 minutes of warm renal ischemia with nephrectomy or control animals underwent sham operation(unilateral nephrectomy). Renal function and survival rates were evaluated on day 0, 1, 2, 3, 5 and 7. Immunofluorescence staining of dendritic cells(DCs), natural killer(NK) cells, macrophages, B cells, CD4+ and CD8+ T cells were measured on day 1 and 7 after renal I/RI. Survival rates dropped below 50% after day 3 in 45 minutes ischemia. Histologic analysis of ischemic kidneys revealed a significant loss of tubular architecture and infiltration of inflammatory cells. DCs, NK cells, macrophages, CD4+ and CD8+ T cells were infiltrated from a day after I/RI depending on ischemia time. Antigen presenting cells(DCs, NK cells or macrophages) and even T cells were infiltrated 24 hours post-I/RI, which is at the time of acute tubular necrosis. During the regeneration phase, not only these cells increased but B cells also appeared in more than 45 minutes ischemia. The numbers of the innate and the adaptive immune cells increased depending on ischemia as well as reperfusion time. These changes of infiltrating cells resulting from each I/RI model show that ischemic time plays a role in activating rejection related immune factors and have consequences on progression of renal disease in transplanted and native kidneys.
Ischemia/reperfusion injury(I/RI) is the major cause of acute renal failure and delayed graft function(DGF) unavoidable in renal transplantation. Enormous studies on ischemia damage playing a role in activating graft rejection factors, such as T cells or macrophages, are being reported. Present study was performed to determine whether ischemia time would play an important role in activating rejection-related factors or not in rat models of I/RI. Male Sprague-Dawley rats were submitted to 30, 45, and 60 minutes of warm renal ischemia with nephrectomy or control animals underwent sham operation(unilateral nephrectomy). Renal function and survival rates were evaluated on day 0, 1, 2, 3, 5 and 7. Immunofluorescence staining of dendritic cells(DCs), natural killer(NK) cells, macrophages, B cells, CD4+ and CD8+ T cells were measured on day 1 and 7 after renal I/RI. Survival rates dropped below 50% after day 3 in 45 minutes ischemia. Histologic analysis of ischemic kidneys revealed a significant loss of tubular architecture and infiltration of inflammatory cells. DCs, NK cells, macrophages, CD4+ and CD8+ T cells were infiltrated from a day after I/RI depending on ischemia time. Antigen presenting cells(DCs, NK cells or macrophages) and even T cells were infiltrated 24 hours post-I/RI, which is at the time of acute tubular necrosis. During the regeneration phase, not only these cells increased but B cells also appeared in more than 45 minutes ischemia. The numbers of the innate and the adaptive immune cells increased depending on ischemia as well as reperfusion time. These changes of infiltrating cells resulting from each I/RI model show that ischemic time plays a role in activating rejection related immune factors and have consequences on progression of renal disease in transplanted and native kidneys.
* AI 자동 식별 결과로 적합하지 않은 문장이 있을 수 있으니, 이용에 유의하시기 바랍니다.
가설 설정
In this study, we investigated whether ischemia time would play an important role in activating rejection related factors or not in rat models of I/RI. Analyzing immune modulation in moderate or severe ischemia at early and later stages of I/ RI would provide us clues for targeting the immune initiation factors to control rejection or DGF in I/RI organ transplantation.
제안 방법
For evaluation of functional recovery, tail bleeds were collected from rats before surgery and at 1, 2, 3, 5 and 7 days after reperfusion. Blood samples were tested for serum creatinine levels (mg/dl) using Spotchem EZ (SP-4430, ARKRAY INC.
이론/모형
Comparison between groups was performed by Dunnet’s test. KaplanMeier analysis was used to analyze the survival rate. P < 0.
성능/효과
In conclusions, expression of immune cells, especially antigen presenting cells, at seven days after I/RI proves that I/RI evoke immune responses. Regardless of reperfusion time, increase in cell numbers in severe ischemia groups over moderate ischemia group shows that ischemic time affects the degree of immune responses.
후속연구
Future study might be needed to analyze cytokines (e.g. IFN-γ, TFN-α, IL-1β and IL-6) for demonstrating the amplified immune reaction.
참고문헌 (24)
Ascon DB, Lopez-Briones S, Liu M, Ascon M, Savransky V, Colvin RB, Soloski MJ, Rabb H. Phenotypic and functional characterization of kidney-infiltrating lymphocytes in renal ischemia reperfusion injury. J Immunol 2006; 177: 3380-3387
Burne MJ, Daniels F, El Ghandour A, Mauiyyedi S, Colvin RB, O'Donnell MP, Rabb H. Identification of the CD4(+) T cell as a major pathogenic factor in ischemic acute renal failure. J Clin Invest 2001; 108: 1283-1290
Burne-Taney MJ, Yokota-Ikeda N, Rabb H. Effects of combined T-and B-cell deficiency on murine ischemia reperfusion injury. Am J Transplant 2005; 5: 1186-1193
Czech KA, Ryan JW, Sagen J, Pappas GD. The influence of xenotransplant immunogenicity and immunosuppression on host MHC expression in the rat CNS. Exp Neurol 1997; 147: 66-83
Dong X, Swaminathan S, Bachman LA, Croatt AJ, Nath KA, Griffin MD. Antigen presentation by dendritic cells in renal lymphnodes is linked to systemic and local injury to the kidney. Kidney Int 2005; 68: 1096-1108
Grigoryev DN, Liu M, Cheadle C, Barnes KC, Rabb H. Genomic profiling of kidney ischemia-reperfusion reveals expression of specific alloimmunity-associated genes: linking "immune" and "nonimmune" injury events. Transplant Proc 2006; 38: 3333-3336
He H, Stone JR, Perkins DL. Analysis of differential immune responses induced by innate and adaptive immunity following transplantation. Immunology 2003; 109: 185-196
Jacobi CA, Ordemann J, Zieren HU, Volk HD, Bauhofer A, Halle E, Muller JM. Increased systemic inflammation after laparotomy vs laparoscopy in an animal model of peritonitis. Arch Surg 1998; 133: 258-262
Penfield JG, Dawidson IA, Ar’Rajab A, Kielar MA, Jeyarajah DR, Lu CY. Syngeneic renal transplantation increases the number of renal dendritic cells in the rat. Transpl Immunol 1999; 7: 197-200
Rabb H, Daniels F, O'Donnell M, Haq M, Saba SR, Keane W, Tang WW. Pathophysiological role of T lymphocytes in renal ischemiareperfusion injury in mice. Am J Physiol 2000; 279: 525-531
Rabb H. The T cell as a bridge between innate and adaptive immune systems: Implications for the kidney. Kidney Int 2002; 61: 1935-1946
Van Putte BP, Kesecioglu J, Hendriks JM, Persy VP, van Marck E, Van Schil PE, De Broe ME. Cellular infiltrates and injury evaluation in a rat model of warm pulmonary ischemia-reperfusion. Crit Care 2005; 9:R1-R8
Ysebaert DK, De Greef KE, Vercauteren SR, Ghielli M, Verpooten GA, Eyskens EJ, De Broe ME. Identification and kinetics of leukocytes after sever ischaemia/reperfusion renal injury. Nephro Dial Transplant. 2000; 15: 1562-1574
Ysebaert DK, De Greef KE, Vercauteren SR, Verhulst A, Kockx M, Verpooten GA, De Broe ME. Effect of immunosuppression on damage, leukocyte infiltration, and regeneration after severe warm ischemia/reprfusion renal inmury. Kidney Int 2003; 64: 864-873
Zhou T, Sun GZ, Zhang MJ, Chen JL, Zhang DQ, Hu QS, Chen YY, Chen N. Role of adhesion molecules and dendritic cells in rat hepatic/renal ischemia？reperfusion injury and anti-adhesive intervention with anti-P-selectin lectin-EGF domain monoclonal antibody, World J. Gastroenterol. 2005; 11: 1005-1010
※ AI-Helper는 부적절한 답변을 할 수 있습니다.