Smith Jennifer, Lai Ping-Chin, Behmoaras Jacques, Roufosse Candice, Bhangal Gurjeet, McDaid John P, Aitman Timothy, Tam Frederick W K, Pusey Charles D, Cook H Terence
Department of Histopathology, Hammersmith Campus, Imperial College London, Du Cane Road, London, UK.
J Am Soc Nephrol. 2007 Jun;18(6):1816-23. doi: 10.1681/ASN.2006070733. Epub 2007 May 2.
The Wistar-Kyoto (WKY) rat shows marked susceptibility to crescentic glomerulonephritis. In the model of nephrotoxic nephritis (NTN) that is induced by a small dose of nephrotoxic globulin, WKY rats developed crescents in 80 +/- 2% of glomeruli at day 10, whereas no crescents were seen in Lewis rats. This was associated with marked increase in monocyte chemoattractant protein-1 synthesis in WKY glomeruli. It was posited whether susceptibility depended on circulating cells or intrinsic renal cells. Bone marrow (BM) isografts from WKY to WKY or Lewis to Lewis did not affect susceptibility to NTN. When BM was transferred from WKY to Lewis rats, crescents developed in 35 +/- 9% of glomeruli 10 d after induction of NTN, indicating that susceptibility could be transferred by BM cells. However, crescents were also seen in WKY rats that were given Lewis marrow. For assessment of the contribution of intrinsic renal cells, kidneys from WKY or Lewis rats were transplanted into F1 animals. In NTN, the ratio of crescents in the transplanted kidney to the native kidney was significantly higher for WKY-to-F1 than for Lewis-to-F1 transplants, demonstrating that the kidney itself also influences susceptibility. Mesangial cell responses were then examined in the two strains. Mesangial cells that were derived from WKY rats synthesized significantly more monocyte chemoattractant protein-1 basally and after stimulation with heat-aggregated rabbit IgG or TNF-alpha. These results show that susceptibility to NTN in the WKY rat depends on both circulating and intrinsic renal cells and that there are genetic differences between the strains in mesangial responses to inflammatory stimuli.
Wistar-Kyoto（WKY）大鼠对新月体性肾小球肾炎表现出明显的易感性。在小剂量肾毒性球蛋白诱导的肾毒性肾炎（NTN）模型中，WKY大鼠在第10天时80±2%的肾小球出现新月体，而Lewis大鼠未见新月体。这与WKY肾小球中单核细胞趋化蛋白-1合成的显著增加有关。有人提出易感性是取决于循环细胞还是肾固有细胞。WKY之间或Lewis之间的骨髓（BM）同种移植不影响对NTN的易感性。当将WKY的BM移植到Lewis大鼠时，NTN诱导后10天，35±9%的肾小球出现新月体，表明易感性可通过BM细胞传递。然而，接受Lewis骨髓的WKY大鼠也出现了新月体。为了评估肾固有细胞的作用，将WKY或Lewis大鼠的肾脏移植到F1动物体内。在NTN中，WKY到F1移植的移植肾与自身肾新月体的比例显著高于Lewis到F1移植，表明肾脏本身也影响易感性。然后检测了这两个品系的系膜细胞反应。源自WKY大鼠的系膜细胞在基础状态下以及在热聚集兔IgG或TNF-α刺激后合成的单核细胞趋化蛋白-1明显更多。这些结果表明，WKY大鼠对NTN的易感性取决于循环细胞和肾固有细胞，并且在系膜对炎症刺激的反应方面品系间存在遗传差异。
