Mast cell-mediated remodeling and fibrinolytic activity protect against fatal glomerulonephritis
Mast cell-mediated remodeling and fibrinolytic activity protect against fatal glomerulonephritis
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DOI：
10.4049/jimmunol.176.9.5607
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发表时间：
2006-05-01
影响因子：
4.4
通讯作者：
Blank, Ulrich
中科院分区：
文献类型：
--
作者：
Kanamaru, Yutaka;Scandiuzzi, Lisa;Blank, Ulrich
肥大细胞在几种炎症性疾病中是有害的；然而，它们的生理作用也越来越被认识到。最近的数据表明，肥大细胞可能也参与了肾脏疾病。因此，我们使用了先天性肥大细胞缺陷的W/W-v小鼠和正常的+/+胎鼠来评估它们在抗肾小球基底膜诱导的肾小球肾炎中的作用。注射抗肾小球基底膜抗体后，由于肾功能迅速恶化，W/W-v小鼠的死亡率明显高于+/+小鼠。W/W-v小鼠肥大细胞群的重建恢复了保护。这与激活Fc-Gamma R无关，因为利用缺乏FCR-Gamma的肥大细胞也可以获得保护。肾脏的比较组织学分析表明，W/W-v小鼠肾功能的恶化是由于存在厚层的内皮下肾小球沉积，而+/+小鼠或肥大细胞重组的W/W-v小鼠的肾功能恶化明显较小。沉积出现在疾病的早期阶段，并持续存在，并伴随着巨噬细胞募集的增强。免疫组织化学分析显示，W/W-v小鼠纤维蛋白和I型胶原含量增加，在疾病异种期也无法维持尿液中高水平的组织型纤溶酶原激活剂和尿型纤溶酶原激活剂活性。我们的结果表明，肥大细胞通过其介导重塑和修复功能在免疫复合体介导的肾小球肾炎中具有保护作用。
Mast cells are detrimental in several inflammatory diseases; however, their physiological roles are also increasingly recognized. Recent data suggest that mast cells may also be involved in renal diseases. We therefore used congenitally mast cell-deficient W/W-v mice and normal +/+ littermates to assess their role in anti-glomerular basement membrane-induced glomerulonephritis. Following administration of-anti-glomerular basement membrane Abs, W/W-v mice exhibited increased mortality as compared with +/+ mice owing to rapid deterioration of renal function. Reconstitution of the mast cell population in W/W-v mice restored protection. This was independent of activating Fc gamma R, as protection was also obtained using mast cells deficient in FcR gamma. Comparative histological analysis of kidneys showed that deterioration of renal function was caused by the presence of thick layers of subendothelial glomerular deposits in W/W-v mice, while +/+ mice or mast cell-reconstituted W/W-v mice showed significantly less. Deposits appeared during the early phase of disease and persisted thereafter, and were accompanied by enhanced macrophage recruitment. Immumohistochemical analysis revealed increased amounts of fibrin and type I collagen in W/W-v mice, which were also unable to maintain high tissue plasminogen activator and urinary-type plasminogen activator activity in urine in the heterologous phase of disease. Our results indicate that mast cells by their ability to mediate remodeling and repair functions are protective in immune complex-mediated glomerulonephritis.