Possible role of complement factor H in podocytes in clearing glomerular subendothelial immune complex deposits
Possible role of complement factor H in podocytes in clearing glomerular subendothelial immune complex deposits
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足细胞中补体因子 H 在清除肾小球内皮下免疫复合物沉积物中的可能作用
DOI：
10.1038/s41598-019-44380-3
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Nagata M.
中科院分区：
文献类型：
--
作者：
Zoshima T;Hara S;Yamagishi M;Pastan I;Matsusaka T;Kawano M;Nagata M.
已知足细胞表达各种补体因子，包括补体因子H（CFH），并促进去除内皮下和上皮下免疫复合物（IC）沉积物。本研究利用足细胞选择性损伤模型NEP 25小鼠和MRL/lpr小鼠建立的产生IgG 3的杂交瘤克隆2B11.3，研究足细胞补体调节在仅内皮下IC沉积中的作用。在免疫毒素（LMB 2）诱导的致死性足细胞损伤（NEP 25/LMB 2）中，与NEP 25/媒介物小鼠相比，在第12天，肾小球CFH和C3 a受体（C3 aR）表达降低。相反，在LMB 2后5天的亚溶解足细胞损伤中，与NEP 25/载体小鼠相比，肾小球CFH和C3 aR表达增加。向NEP 25小鼠腹腔内注射2B11.3杂交瘤（NEP 25/杂交瘤）导致IC沉积限于与未改变的CFH表达相关的内皮下区域。与NEP 25/杂交瘤相比，足细胞亚溶解性损伤的NEP 25/杂交瘤小鼠（NEP 25/杂交瘤/LMB 2）导致肾小球CFH表达增加（1.7倍），伴有内皮下IC沉积减少。免疫组化显示CFH主要表达于NEP 25/hybridoma/LMB 2的足细胞。此外，嘌呤霉素诱导的足细胞亚溶解性损伤促进体外永生化小鼠足细胞CFH表达。这些结果表明，在响应亚溶解水平的损伤，足细胞诱导CFH表达局部和清除内皮下IC存款。
Podocytes are known to express various complement factors including complement factor H (CFH) and to promote the removal of both subendothelial and subepithelial immune complex (IC) deposits. Using podocyte-selective injury model NEP25 mice and an IgG3-producing hybridoma clone 2B11.3 established by MRL/lpr mice, the present study investigated the role of podocyte complement regulation in only subendothelial IC deposition. In immunotoxin (LMB2) induced fatal podocyte injury (NEP25/LMB2) at day 12, glomerular CFH and C3a receptor (C3aR) expression was decreased as compared with NEP25/vehicle mice. In contrast, in sublytic podocyte injury 5 days after LMB2, glomerular CFH and C3aR expression was increased as compared with NEP25/vehicle mice. Intra-abdominal injection of 2B11.3 hybridoma to NEP25 mice (NEP25/hybridoma) caused IC deposition limited to the subendothelial area associated with unaltered CFH expression. NEP25/hybridoma mice with sublytic podocyte injury (NEP25/hybridoma/LMB2) resulted in increased glomerular CFH expression (1.7-fold) accompanied by decreased subendothelial IC deposition, as compared with NEP25/hybridoma. Immunostaining revealed that CFH was dominantly expressed in podocytes of NEP25/hybridoma/LMB2. In addition, puromycin-induced sublytic podocyte injury promoted CFH expression in immortalized mouse podocytesin vitro. These results suggest that in response to sublytic levels of injury, podocyte induced CFH expression locally and clearance of subendothelial IC deposits.
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影响因子：
6
作者：
J. Itoh;Masato Nose;Satoru Takahashi;Masao Ono;S. Terasaki;Emiko Kondoh;Masahisa Kyogoku
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影响因子：
3.5
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通讯作者：
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新的补体功能：抗原抗体聚集体的溶解。
DOI：
--
发表时间：
1975
影响因子：
11.1
作者：
G. Miller;V. Nussenzweig
通讯作者：
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影响因子：
6
作者：
Y. Fujigaki;M. Nagase;N. Honda
通讯作者：
N. Honda
影响因子：
13.6
作者：
Bao, Lihua;Haas, Mark;Quigg, Richard J.
通讯作者：
Quigg, Richard J.