The cytokine-adhesion molecule cascade in ischemia/reperfusion injury of the rat kidney - Inhibition by a soluble P-selectin ligand
The cytokine-adhesion molecule cascade in ischemia/reperfusion injury of the rat kidney - Inhibition by a soluble P-selectin ligand
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DOI：
10.1172/jci119457
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发表时间：
1997-06-01
影响因子：
15.9
通讯作者：
Tilney, NL
中科院分区：
文献类型：
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作者：
Takada, M;Nadeau, KC;Tilney, NL
缺血/再灌注（I/R）损伤与肾移植可能会影响移植肾功能的早期和晚期变化。在单侧肾切除大鼠中，检查了原始（小于或等于7天）的热缺血和原位灌注冷缺血事件。早期粘附分子E-选择素mRNA表达在6 h内达到峰值;中性粒细胞平行浸润。T细胞和巨噬细胞进入损伤的肾脏2-5 d;相关的MHC II类抗原表达上调表明器官的免疫原性增加。Th 1产物（IL-2、TNF α、IFN γ）和巨噬细胞相关产物（IL-1、IL-6、TGF β）在2 d后仍保持高表达。为了直接检测选择素在I/R损伤中的作用，使用可溶性P-选择素糖蛋白配体（sPSGL），用5 μ g溶于UW溶液的sPSGL原位灌注缺血肾;再灌注后3小时静脉内施用50 μ g。E-选择素mRNA保持在基线水平，白细胞在整个7天期间没有浸润损伤的器官，其相关产物被明显抑制。II类表达没有增加。未发生继发于I/R的肾功能损害。应用可溶性P-和E-选择素配体可预防I/R损伤的早期改变。这可以减少移植后随后的宿主炎症反应。
Ischemia/reperfusion (I/R) injury associated with renal transplantation may influence both early graft function and late changes. The initial (less than or equal to 7 d) events of warm and in situ perfused cold ischemia of native kidneys in uninephrectomized rats were examined. mRNA expression of the early adhesion molecule, E-selectin, peaked within 6 h; PMNs infiltrated in parallel. T cells and macrophages entered the injured kidney by 2-5 d; the associated upregulation of MHC class II antigen expression suggested increased immunogenicity of the organ. Th1 products (IL-2, TNF alpha, IFN gamma) and macrophage-associated products (IL-1, IL-6, TGF beta) remained highly expressed after 2 d. To examine directly the effects of selectins in I/R injury, a soluble P-selectin glycoprotein ligand (sPSGL) was used, Ischemic kidneys were perfused in situ with 5 mu g of sPSGL in UW solution; 50 mu g was administered intravenously 3 h after reperfusion. E-selectin mRNA remained at baseline, leukocytes did not infiltrate the injured organs throughout the 7-d period, and their associated products were markedly inhibited. Class II expression did not increase. No renal dysfunction secondary to I/R occurred. The early changes of I/R injury may be prevented by treatment with soluble P- and E-selectin ligand. This may reduce subsequent host inflammatory responses after transplantation.