Mechanisms of chronic renal allograft rejection. II. Progressive allograft glomerulopathy in miniature swine
Mechanisms of chronic renal allograft rejection. II. Progressive allograft glomerulopathy in miniature swine
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DOI：
10.1097/01.lab.0000017370.74529.89
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发表时间：
2002-06-01
影响因子：
5
通讯作者：
Colvin, RB
中科院分区：
文献类型：
--
作者：
Shimizu, A;Yamada, K;Colvin, RB
我们已经报道，在用环孢菌素A治疗12天的胸腺切除的小型猪中，主要组织相容性复合物I类不匹配的肾同种异体移植物或者进展为慢性排斥（进展组; n = 4）或者在急性排斥后耐受（恢复组; n = 4）。两种类型的肾小球病，称为急性和慢性同种异体移植物肾小球病，发生在同种异体移植物在这个模型中。对两组肾活检标本进行形态学和免疫组化研究，以探讨急性和慢性移植物肾小球病的发病机制。在急性排斥反应中，两组在第18天均发生急性同种异体移植物肾小球病，伴有抗体沉积以及T细胞和巨噬细胞浸润。原位DNA缺口末端标记（TUNEL）+损伤的肾小球内皮细胞出现在早期阶段，其次是肾小球毛细血管网络的破坏，节段性系膜溶解。此后，在进展组中，在慢性排斥反应的发展过程中，急性同种异体移植物肾小球病进展为慢性同种异体移植物肾小球病。这一过程与肾小球中持续的T细胞和巨噬细胞浸润、抗体沉积和TUNEL+肾小球内皮损伤有关。在第100天仍观察到毛细血管修复受损、系膜细胞增殖和活化，以及系膜基质蓄积和肾小球基底膜复制。相反，在恢复组中，急性同种异体移植物肾小球病在第100天恢复，与细胞浸润消退和抗体沉积减少相关。我们的结论是，急性和持续的细胞和抗体介导的排斥反应对肾小球内皮细胞是关键的致病因素，急性同种异体移植物肾小球病和慢性同种异体移植物肾小球病的进展。毛细血管修复受损以及内皮细胞和系膜细胞表型改变也是慢性同种异体移植物肾小球病发生的原因。随着免疫耐受的发展，肾小球炎症消退后，急性同种异体移植物肾小球病可基本恢复。
we have reported that in thymectomized miniature swine treated with a 12-day course of cyclosporin A that major histocompatibility complex class I-mismatched renal allografts either progress to chronic rejection (progression group; n = 4) or tolerance after acute rejection (recovery group; n = 4). Two types of glomerulopathies, termed acute and chronic allograft glomerulopathy, occur in allografts in this model. Morphological and immunohistochemical studies were performed on serial renal biopsies from both groups to examine the pathogenic mechanisms of acute and chronic allograft glomerulopathy. In acute rejection, acute allograft glomerulopathy developed in both groups by Day 18, with antibody deposition and T cell and macrophage infiltration. In situ DNA nick end-labeling (TUNEL)+ injured glomerular endothelial cells appeared from the early phase, followed by destruction of the glomerular capillary network with segmental mesangiolysis. Thereafter, in the progression group, acute allograft glomerulopathy progressed to chronic allograft glomerulopathy during the development of chronic rejection. This process was associated with persistent T cell and macrophage infiltration, antibody deposition, and TUNEL+ glomerular endothelial injury in the glomeruli. Impaired capillary repair, mesangial cell proliferation, and activation were still noted at Day 100, together with accumulation of mesangial matrix and duplication of glomerular basement membrane. In contrast, in the recovery group, acute allograft glomerulopathy recovered by Day 100, associated with the resolution of cellular infiltration and reduction of antibody deposition. We conclude that the acute and persistent cell- and antibody-mediated rejection against glomerular endothelial cells is the key pathogenic determinant of acute allograft glomerulopathy and progression toward chronic allograft glomerulopathy. Impaired capillary repair and phenotypic change of endothelial and mesangial cells also contribute to the development of chronic allograft glomerulopathy. With the development of tolerance, substantial recovery of acute allograft glomerulopathy can occur after the resolution of glomerular inflammation.