Ischemia-reperfusion injury in renal transplantation is independent of the immunologic background

被引:47
作者
Dragun, D
Hoff, U
Park, JK
Qun, Y
Schneider, W
Luft, FC
Haller, H
机构
[1] Humboldt Univ, Charite, Fac Med, Max Delbruck Ctr Mol Med,Franz Volhard Clin, D-13122 Berlin, Germany
[2] Hannover Med Sch, D-3000 Hannover, Germany
关键词
adhesion molecules; inflammation; endothelium; monocytes; macrophages; graft failure;
D O I
10.1046/j.1523-1755.2000.00390.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. Adhesion molecule expression is important to early transplant failure. However, whether or not adhesion molecule-facilitated inflammation is antigen-dependent is unknown. We tested this hypothesis. Methods. Rat renal grafts were four-hours cold-preserved in University of Wisconsin (UW) solution, transplanted to syngeneic or allogeneic recipients, and harvested after 2, 6, 12, 24, and 48 hours and after 1 week. The first allogeneic group receive no immunosuppression; two additional groups received either low (1.5 mg/kg) or standard (5 mg/kg) cyclosporine A (CsA). Renal function and morphology were determined; frozen sections were immunostained for P-selectin, L-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), leukocyte function associated molecule-1 (LFA-1), very late antigen-4 (VLA-4), as well as for neutrophils and monocytes. Results. Selectins increased rapidly at 2 hours and quickly decreased by 12 hours. While P-selectin was expressed on vasculature, L-selectin was found on inflammatory cells. Neutrophil influx and that of LFA-l-positive cells occurred early, peaked between 12 and 24 hours, and paralleled the maximal impairment in renal function. ICAM-1 and PECAM-1 showed similar kinetics and a diffuse distribution. VCAM-1 increased more slowly after 12 hours, peaked at 24 hours, and was localized predominantly on the endothelium of elastic vessels. Between 24 hours and 1 week, all grafts progressively developed dense VLA-Il-positive monocytic infiltrates adjacent to vessels expressing VCAM-1. Functional, morphological, and immunohistochemical parameters did not differ between isografts and allografts at one week. However, by day 10, allografts showed severe vascular and cellular rejection, while injury in isografts resolved. Immunosuppression with CsA did not reverse the inflammation induced by ischemia-reperfusion injury. Conclusions. The early inflammation after ischemia-reperfusion injury is largely independent of the immunologic back-ground. We suggest that initial injury prevention should receive the highest priority.
引用
收藏
页码:2166 / 2177
页数:12
相关论文
共 29 条
[1]   ENDOTHELIAL-LEUKOCYTE ADHESION MOLECULES IN HUMAN-DISEASE [J].
BEVILACQUA, MP ;
NELSON, RM ;
MANNORI, G ;
CECCONI, O .
ANNUAL REVIEW OF MEDICINE, 1994, 45 :361-378
[2]   ICAM-1 antisense oligodesoxynucleotides prevent reperfusion injury and enhance immediate graft function in renal transplantation [J].
Dragun, D ;
Tullius, SG ;
Park, JK ;
Maasch, C ;
Lukitsch, I ;
Lippoldt, A ;
Gross, V ;
Luft, FC ;
Haller, H .
KIDNEY INTERNATIONAL, 1998, 54 (02) :590-602
[3]   Inhibition of intercellular adhesion molecule-1 with antisense deoxynucleotides prolongs renal isograft survival in the rat [J].
Dragun, D ;
Lukitsch, I ;
Tullius, SG ;
Qun, Y ;
Park, JK ;
Schneider, W ;
Luft, FC ;
Haller, H .
KIDNEY INTERNATIONAL, 1998, 54 (06) :2113-2122
[4]   Cell adhesion molecules in clinical renal transplantation [J].
Fuggle, SV ;
Koo, DDH .
TRANSPLANTATION, 1998, 65 (06) :763-769
[5]   VARIATION IN EXPRESSION OF ENDOTHELIAL ADHESION MOLECULES IN PRETRANSPLANT AND TRANSPLANTED KIDNEYS - CORRELATION WITH INTRAGRAFT EVENTS [J].
FUGGLE, SV ;
SANDERSON, JB ;
GRAY, DWR ;
RICHARDSON, A ;
MORRIS, PJ .
TRANSPLANTATION, 1993, 55 (01) :117-123
[6]   Inflammatory cells in renal regeneration [J].
Ghielli, M ;
Verstrepen, WA ;
Nouwen, EJ ;
DeBroe, ME .
RENAL FAILURE, 1996, 18 (03) :355-375
[7]  
Granger DN, 1997, AM J PHYSIOL-GASTR L, V273, pG982, DOI 10.1152/ajpgi.1997.273.5.G982
[8]   TARGETED DISRUPTION OF THE MURINE VCAM1 GENE - ESSENTIAL ROLE OF VCAM-1 IN CHORIOALLANTOIC FUSION AND PLACENTATION [J].
GURTNER, GC ;
DAVIS, V ;
LI, HM ;
MCCOY, MJ ;
SHARPE, A ;
CYBULSKY, MI .
GENES & DEVELOPMENT, 1995, 9 (01) :1-14
[9]   Antisense oligonucleotides for ICAM-1 attenuate reperfusion injury and renal failure in the rat [J].
Haller, H ;
Dragun, D ;
Miethke, A ;
Park, JK ;
Weis, A ;
Lippoldt, A ;
Gross, V ;
Luft, FC .
KIDNEY INTERNATIONAL, 1996, 50 (02) :473-480
[10]  
HALLORAN PF, 1997, TRANSPLANT P, V29, P78