Araki Motoo, Fahmy Nader, Zhou Lingmei, Kumon Hiromi, Krishnamurthi Venkatesh, Goldfarb David, Modlin Charles, Flechner Stuart, Novick Andrew C, Fairchild Robert L
Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Transplantation. 2006 Mar 15;81(5):783-8. doi: 10.1097/01.tp.0000198736.69527.32.
Ischemia/reperfusion injury is an inherent consequence of solid organ transplantation that increases tissue inflammation and negatively impacts organ transplant function and survival. This study investigated the expression levels of chemokine and chemokine receptor genes in living versus cadaver donor renal allografts before and after reperfusion.
This study involved 39 renal transplant patients (19 cadaveric and 20 living donor). The ischemia biopsy was taken just before graft declamping and the reperfusion biopsy 30 min after declamping. Whole-cell RNA was isolated and chemokine (IL-8, CCL2/MCP-1, CXCL10/IP-10 and CCL5/RANTES) and chemokine receptor (CCR2 and CCR5) expression was tested by quantitative PCR.
Just prior to declamping, ischemic cadaveric donor grafts had higher expression of CXCL10/IP-10 but not IL-8 or CCL2/MCP-1 than living donor grafts. IL-8 expression increased 50% from ischemia to reperfusion in living donor grafts but increased more than 13-fold during reperfusion of cadaver donor grafts. Increased total ischemia time induced greater IL-8 expression during reperfusion. MCP-1 expression also increased during reperfusion of living and cadaver donor grafts but differences were not observed between the two groups of grafts. RANTES, CCR2, and CCR5 expression did not change in ischemic vs. reperfusion biopsies.
The expression of chemokines directing neutrophil and macrophage recruitment increases during reperfusion of living and cadaveric donor renal allografts. Expression levels of IL-8 correlate with the ischemic time imposed on the renal graft. Early tissue injury may be attenuated by strategies antagonizing chemokines directing the recruitment of neutrophils and macrophages into kidney grafts.
缺血/再灌注损伤是实体器官移植的一个固有后果，它会加剧组织炎症，并对器官移植功能和存活产生负面影响。本研究调查了再灌注前后活体供肾与尸体供肾同种异体移植中趋化因子和趋化因子受体基因的表达水平。
本研究纳入了39例肾移植患者（19例尸体供肾和20例活体供肾）。在移植肾松开血管夹前进行缺血活检，松开血管夹30分钟后进行再灌注活检。分离全细胞RNA，通过定量PCR检测趋化因子（白细胞介素-8、CCL2/单核细胞趋化蛋白-1、CXCL10/干扰素诱导蛋白-10和CCL5/调节激活正常T细胞表达和分泌因子）和趋化因子受体（CCR2和CCR5）的表达。
在松开血管夹前，缺血的尸体供肾移植中CXCL10/干扰素诱导蛋白-10的表达高于活体供肾移植，但白细胞介素-8或CCL2/单核细胞趋化蛋白-1的表达并非如此。活体供肾移植中白细胞介素-8的表达从缺血到再灌注增加了50%，但在尸体供肾移植再灌注期间增加了13倍以上。总缺血时间增加导致再灌注期间白细胞介素-8表达增加。单核细胞趋化蛋白-1的表达在活体和尸体供肾移植再灌注期间也增加，但两组移植之间未观察到差异。在缺血与再灌注活检中，调节激活正常T细胞表达和分泌因子、CCR2和CCR5的表达没有变化。
在活体和尸体供肾同种异体移植再灌注期间，指导中性粒细胞和巨噬细胞募集的趋化因子表达增加。白细胞介素-8的表达水平与施加于肾移植的缺血时间相关。通过拮抗趋化因子的策略，早期组织损伤可能会减轻，趋化因子可指导中性粒细胞和巨噬细胞募集到肾移植中。
