Khan Fahima, Yamakami Kazuo, Mahmood Javed, Li Bing, Kikuchi Tamami, Kumagai Naoki, Morioka Tetsuo, Yoshizawa Nobuyuki, Oite Takashi
Department of Cellular Physiology, Institute of Nephrology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Nephron Exp Nephrol. 2007;105(2):e53-64. doi: 10.1159/000097840. Epub 2006 Dec 8.
Acute post-streptococcal glomerulonephritis (APSGN) is induced by glomerular deposition of nephritogenic streptococcal antigen-antibody complexes. Recently, a streptococcal antigen, nephritis-associated plasminogen receptor (NAPlr) was purified from ruptured streptococcal cell supernatants (RCS). However, the cellular and molecular mechanisms of NAPlr action on the glomerular vas culature are still unknown.
Expression of cell adhesion molecules were measured by cellular ELISA (enzyme-linked immunosorbent assay), immunofluorescence microscopy and Western blot analysis.
RCS and NAPlr significantly decreased the PECAM-1 expression in human glomerular endothelial cells (HGECs) as compared to that in the control cells. Plasminogen treatment reversed the RCS or NAPlr-induced decrease of PECAM-1 expression and increase of MCP-1 expression. Immunofluorescent microscopy and Western blot analysis also showed that PECAM-1 expression in HGECs was downregulated upon treatment with RCS or NAPlr and this effect was reversed by plasminogen treatment. Furthermore, we found that tumor necrosis factor-alpha production in culture medium of HGECs was increased at the lower level when the culture system was treated with RCS.
RCS and NAPlr modulated PECAM-1 expression and MCP-1 production in HGECs, indicating the involvement of NAPlr in inflammatory cell accumulation in glomerular tufts and functional abnormality of glomerular microvasculature such as hyperpermeability.
急性链球菌感染后肾小球肾炎（APSGN）是由致肾炎性链球菌抗原 - 抗体复合物在肾小球沉积所诱发。最近，一种链球菌抗原，即肾炎相关纤溶酶原受体（NAPlr），已从破裂的链球菌细胞上清液（RCS）中纯化出来。然而，NAPlr对肾小球血管系统作用的细胞和分子机制仍不清楚。
通过细胞酶联免疫吸附测定（ELISA）、免疫荧光显微镜检查和蛋白质印迹分析来检测细胞黏附分子的表达。
与对照细胞相比，RCS和NAPlr显著降低了人肾小球内皮细胞（HGECs）中血小板内皮细胞黏附分子 - 1（PECAM - 1）的表达。纤溶酶原处理可逆转RCS或NAPlr诱导的PECAM - 1表达降低以及单核细胞趋化蛋白 - 1（MCP - 1）表达增加。免疫荧光显微镜检查和蛋白质印迹分析还显示，用RCS或NAPlr处理后HGECs中PECAM - 1表达下调，而纤溶酶原处理可逆转这种效应。此外，我们发现当培养系统用RCS处理时，HGECs培养基中肿瘤坏死因子 - α的产生在较低水平增加。
RCS和NAPlr调节HGECs中PECAM - 1的表达和MCP - 1的产生，表明NAPlr参与了肾小球毛细血管襻中炎症细胞的积聚以及肾小球微血管功能异常，如高通透性。
