Neointimal and tubulointerstitial infiltration by recipient mesenchymal cells in chronic renal-allograft rejection.

Neointimal and tubulointerstitial infiltration by recipient mesenchymal cells in chronic renal-allograft rejection.
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DOI:
10.1056/nejm200107123450203
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发表时间:
2001-07-12
影响因子:
158.5
通讯作者:
Rush, DN
Rush, DN
中科院分区:
医学1区
文献类型:
--
作者:
Grimm, PC;Nickerson, P;Rush, DN

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背景资料:组织重塑依赖于间充质细胞(成纤维细胞和肌成纤维细胞),是慢性肾移植排斥反应的一个突出特征。目前还不知道是否参与重塑的间充质细胞起源于本地或从循环precursor cells.Methods:我们获得了肾移植活检标本,从6名男性受体的同种异体移植物从女性供体,4名女性受体的同种异体移植物从男性供体,两名男性受体的同种异体移植物从男性供体,和两名女性受体的同种异体移植物从女性供体。所有移植物均发生慢性排斥反应。我们用免疫组化方法,以确定间充质细胞与平滑肌α-肌动蛋白和原位杂交,以确定间充质细胞与Y染色体DNA.Results:没有Y染色体体被确定在两个肾移植标本中,供者和受者都是女性的情况下。在两个供者和受者都是男性的肾移植标本中,大约40%的间充质细胞含有Y染色体体。在供者为女性而受者为男性的6个样本中,新生内膜中34+/-16%的间充质细胞、外膜中38+/-12%的间充质细胞和内膜中30+/-7%的间充质细胞含有Y染色体标记,表明它们来源于受者而不是供者。在供者为男性而受者为女性的四个肾移植标本中,相应的数值分别为24+/-15%、33+/-9%和23+/-8%,表明供者间充质细胞群持续存在。结论:在经历慢性排斥反应的同种异体肾移植物的血管和间质中存在宿主来源的间充质细胞,证据表明循环间充质前体细胞具有迁移到炎症区域的潜力。(新英格兰医学杂志2001;345:93-7。)版权所有(C)2001马萨诸塞州医学会。
Background: Tissue remodeling depends on mesenchymal cells (fibroblasts and myofibroblasts) and is a prominent feature of chronic renal-transplant rejection. It is not known whether the mesenchymal cells that participate in remodeling originate locally or from circulating precursor cells.Methods: We obtained biopsy specimens of renal allografts from six male recipients of an allograft from a female donor, four female recipients of an allograft from a male donor, two male recipients of an allograft from a male donor, and two female recipients of an allograft from a female donor. All the allografts were undergoing chronic rejection. We used immunohistochemical methods to identify mesenchymal cells with smooth-muscle alpha- actin and in situ hybridization to identify mesenchymal cells with Y-chromosome DNA.Results: No Y-chromosome bodies were identified in the case of the two renal-allograft specimens in which both the donor and the recipient were female. In the case of the two renal-allograft specimens in which both the donor and the recipient were male, approximately 40 percent of mesenchymal cells contained a Y-chromosome body. In the case of the six specimens in which the donor was female and the recipient was male, a mean (+/-SD) of 34+/-16 percent of mesenchymal cells in the neointima, 38+/-12 percent of such cells in the adventitia, and 30+/-7 percent of such cells in the interstitium contained the Y-chromosomal marker, indicating that they originated from the recipient rather than the donor. In the case of the four renal-allograft specimens in which the donor was male and the recipient was female, the respective values were 24+/-15 percent, 33+/-9 percent, and 23+/-8 percent, indicating a persistent population of donor mesenchymal cells.Conclusions: The presence of mesenchymal cells of host origin in the vascular and interstitial compartments of renal allografts undergoing chronic rejection provides evidence that a circulating mesenchymal precursor cell has the potential to migrate to areas of inflammation. (N Engl J Med 2001;345:93-7.) Copyright (C) 2001 Massachusetts Medical Society.