Transfer of lymphocytes from mice with renal ischemia can induce albuminuria in naive mice: a possible mechanism linking early injury and progressive renal disease?
Transfer of lymphocytes from mice with renal ischemia can induce albuminuria in naive mice: a possible mechanism linking early injury and progressive renal disease?
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DOI：
10.1152/ajprenal.00229.2005
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发表时间：
2006-11-01
影响因子：
4.2
通讯作者：
Rabb, Hamid
中科院分区：
文献类型：
--
作者：
Burne-Taney, Melissa J.;Liu, Manchang;Rabb, Hamid
严重缺血再灌注损伤（IRI）易导致患者和实验性肾功能长期受损，其机制尚不清楚。鉴于新出现的证据表明淋巴细胞参与了IRI后肾、肝和肺早期损伤的发病机制，我们假设肾IRI可能会释放或暴露正常隔离的抗原，导致抗原识别淋巴细胞增殖。这反过来又会直接参与进行性肾损伤。为了验证这一假设，我们纯化了C57 BL/6小鼠脾淋巴细胞严重肾IRI或假手术6周后缺血，并将这些细胞转移到正常小鼠。患有IRI的供体小鼠具有显著的纤维化和细胞炎症。对受体小鼠进行6或12周的随访。发现供体淋巴细胞运输到受体肾中。移植后12周，与来自假手术小鼠的淋巴细胞相比，来自接受了IRI-primed淋巴细胞的小鼠的肾脏表现出显著增加的尿白蛋白排泄。与接受假手术小鼠淋巴细胞的小鼠相比，接受IRI小鼠淋巴细胞转移的小鼠脾脏CD 3（+）、CD 4（+）、CD 3（+）CD 25（+）和CD 4（+）CD 44（+）计数显著增加。这些数据表明，来自IRI小鼠的淋巴细胞可以运输到受体肾脏并直接介导白蛋白尿。这些数据确定了一种新的机制，通过这种机制，初始肾损伤易导致长期功能障碍，并确定淋巴细胞作为进行性肾脏疾病的潜在治疗靶点。
Severe ischemia-reperfusion injury (IRI) predisposes to long-term impairment in kidney function both in patients and experimentally through unknown mechanisms. Given emerging evidence implicating lymphocytes in the pathogenesis of early injury to kidney, liver, and lung after IRI, we hypothesized that kidney IRI would potentially release or expose normally sequestered antigens that would lead to proliferation of antigen-recognizing lymphocytes. This, in turn, would directly participate in progressive kidney injury. To test this hypothesis, we purified splenic lymphocytes from C57BL/6 mice with severe renal IRI or sham operation 6 wk postischemia and transferred these cells to normal mice. Donor mice with IRI had significant fibrosis and cellular inflammation. The recipient mice were followed for 6 or 12 wk. Donor lymphocytes were found to traffic into recipient kidney. Twelve weeks after transfer, kidneys from mice which received IRI-primed lymphocytes exhibited significantly increased urinary albumin excretion compared with lymphocytes from sham mice. Splenic CD3(+), CD4(+), CD3(+)CD25(+), and CD4(+)CD44(+) counts were significantly increased in mice after lymphocyte transfer from IRI mice vs. mice with lymphocytes from sham mice. These data demonstrate that lymphocytes from IRI mice can traffic to recipient kidney and directly mediate albuminuria. These data identify a novel mechanism by which initial kidney injury predisposes to long-term dysfunction and identify lymphocytes as potential therapeutic targets for progressive renal diseases.