한국임상수의학회지 (Journal of Veterinary Clinics)

  • 제26권2호
  • /
  • Pages.138-143
  • /
  • 2009
  • /
  • 1598-298X(pISSN)
  • /
  • 2384-0749(eISSN)
한국임상수의학회 (The Korean Society of Veterinary Clinics)
권호 표지

허혈 시간과 거부반응 관련 면역반응

Ischemic Time Associated with Activation of Rejection-Related Immune Responses

  • 남현숙 (강원대학교 수의학부대학 외과교실) ;
  • 최진영 (강원대학교 수의학부대학 외과교실) ;
  • 김윤태 (강원대학교 수의학부대학 외과교실) ;
  • 강경선 (서울대학교 수의과대학 공중보건학교실, 성체줄기세포 연구소) ;
  • 권혁무 (강원대학교 수의학부대학 외과교실) ;
  • 홍종해 (강원대학교 수의학부대학 외과교실) ;
  • 김두 (강원대학교 수의학부대학 외과교실) ;
  • 한태욱 (강원대학교 수의학부대학 외과교실) ;
  • 문태영 (강원대학교 한방보건복지대학 응급구조학과) ;
  • 김지희 (강원대학교 한방보건복지대학 응급구조학과) ;
  • 조병렬 (강원대학교 의과대학 순환기내과) ;
  • 우흥명 (강원대학교 수의학부대학 외과교실)
  • Nam, Hyun-Suk (School of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Choi, Jin-Yeung (School of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Kim, Yoon-Tai (School of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Kang, Kyung-Sun (Adult Stem Cell Research, College of Veterinary Medicine, Seoul National University) ;
  • Kwon, Hyuk-Moo (School of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Hong, Chong-Hae (School of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Kim, Doo (School of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Han, Tae-Wook (School of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Moon, Tae-Young (College of Oriental Medicine, Kangwon National University) ;
  • Kim, Jee-Hee (College of Oriental Medicine, Kangwon National University) ;
  • Cho, Byung-Ryul (College of Medicine, Kangwon National University) ;
  • Woo, Heung-Myong (School of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University)
  • 발행 : 2009.04.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

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 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.

키워드

참고문헌

  1. 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 https://doi.org/10.4049/jimmunol.177.5.3380
  2. Bonventre JV, Zuk A. Ischemic acute renal failure: an inflammatory disease? Kidney Int 2004; 66: 480-485 https://doi.org/10.1111/j.1523-1755.2004.761_2.x
  3. Boros P, Bromberg JS. New cellular and molecular immune pathways in ischemia/reperfusion injury. Am J Transplant 2006; 6: 652-658 https://doi.org/10.1111/j.1600-6143.2005.01228.x
  4. 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 https://doi.org/10.1172/JCI200112080
  5. Burne-Taney MJ, Ascon DB, Daniels F, Racusen L, Baldwin W, Rabb H. B cell dificiency confers protection from renal ischemia reperfusion injury. J Immunol 2003; 171: 3210-3215 https://doi.org/10.4049/jimmunol.171.6.3210
  6. 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 https://doi.org/10.1111/j.1600-6143.2005.00815.x
  7. 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 https://doi.org/10.1006/exnr.1997.6589
  8. 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 https://doi.org/10.1111/j.1523-1755.2005.00502.x
  9. 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 https://doi.org/10.1016/j.transproceed.2006.10.129
  10. He H, Stone JR, Perkins DL. Analysis of differential immune responses induced by innate and adaptive immunity following transplantation. Immunology 2003; 109: 185-196 https://doi.org/10.1046/j.1365-2567.2003.01641.x
  11. Huang Y, Rabb H, Womer KL. Ischemia-reperfusion and immediate T cell responses. Cell Immunol 2007; 248: 4-11 https://doi.org/10.1016/j.cellimm.2007.03.009
  12. Jacobi CA, Ordemann J, Zieren HU, Volk HD, Bauhofer A, Halle E, Müller JM. Increased systemic inflammation after laparotomy vs laparoscopy in an animal model of peritonitis. Arch Surg 1998; 133: 258-262 https://doi.org/10.1001/archsurg.133.3.258
  13. 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 https://doi.org/10.1016/S0966-3274(99)80002-1
  14. Portilla D, Okusa MD. T cells and T-cell receptors in acute renal failure. Kidney Int 2006; 69: 208-210 https://doi.org/10.1038/sj.ki.5000128
  15. 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
  16. Rabb H. The T cell as a bridge between innate and adaptive immune systems: Implications for the kidney. Kidney Int 2002; 61: 1935-1946 https://doi.org/10.1046/j.1523-1755.2002.00378.x
  17. Thurman JM. Triggers of inflammation after renal ischemia/ reperfusion. Clin Immunol 2007; 123: 7-13 https://doi.org/10.1016/j.clim.2006.09.008
  18. Tilney NL, Guttmann RD. Effects of initial ischemia/reperfusion injury on the transplanted kidney. Transplantation 1997; 64: 945-947 https://doi.org/10.1097/00007890-199710150-00001
  19. Uccelli A, Moretta L, Pistoia V. Immunoregulatory function of mesenchymal stem cells. Eur J Immunol 2006; 36: 2566-2573 https://doi.org/10.1002/eji.200636416
  20. 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 https://doi.org/10.1186/cc2992
  21. 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 https://doi.org/10.1093/ndt/15.10.1562
  22. 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 https://doi.org/10.1046/j.1523-1755.2003.00150.x
  23. 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 https://doi.org/10.3748/wjg.v11.i7.1005
  24. Zwacka RM, Zhang Y, Halldorson J, Schlossberg H, Dudus L, Engelhardt JF. CD4 (+) T lymphocytes mediate ischemia/ reperfusion-induced inflammatory responses in mouse liver. J Clin Invest 1997; 15:279-89 https://doi.org/10.1172/JCI119533