C5b-9 membrane attack complex mediates endothelial cell apoptosis in experimental glomerulonephritis
C5b-9 membrane attack complex mediates endothelial cell apoptosis in experimental glomerulonephritis
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DOI：
10.1152/ajprenal.2000.278.5.f747
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发表时间：
2000-05-01
影响因子：
4.2
通讯作者：
Johnson, RJ
中科院分区：
文献类型：
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作者：
Hughes, J;Nangaku, M;Johnson, RJ
我们研究了C5 b-9膜攻击复合物在两种炎症性肾小球肾炎（GN）模型中的作用，这两种模型是由压电病毒-葛兰素（PVG）补体充足大鼠（C+）、CG缺陷大鼠（C6-）和系统性补体耗竭与眼镜蛇毒因子（CVF）引起的急性肾小球内皮损伤引起的。通过进行左肾切除术并选择性灌注右肾（1）凝集素伴刀豆球蛋白A（Con A），随后是补体固定抗Con A（Con A GN）或2）纯化的补体固定山羊抗大鼠肾小球内皮细胞（GEN）抗体[免疫介导的血栓性微血管病（ITM）]诱导GN。在两种模型中，在C+动物中检测到相当水平的GEN细胞凋亡。CVF给药使GEN凋亡减少10- 12倍。GEN凋亡是C5 b-9依赖性的，因为PVG C6-大鼠受到保护免于GEN损失。此外，在ITM中通过用抗CD 59抗体肾灌注对细胞表面补体调节蛋白CD 59的功能抑制导致GEN凋亡增加3.5倍。最后，在Con A GN中，GEN凋亡的废除保护了内皮完整性和肾功能。这项研究表明，C5 b-9在实验性炎症GN中诱导GEN凋亡的特定作用，这一发现与抗内皮细胞抗体存在相关的疾病有关。
We studied the role of the C5b-9 membrane attack complex in two models of inflammatory glomerulonephritis (GN) initiated by acute glomerular endothelial injury in Piebold-viral-Glaxo (PVG) complement-sufficient rats (C+), CG-deficient rats (C6-), and rats systematically depleted of complement with cobra venom factor (CVF). GN was induced by performing a left nephrectomy and selectively perfusing the right kidney with either 1) the lectin concanavalin A (Con A) followed by complement-fixing anti-Con A (Con A GN) or 2) purified complement-fixing goat anti-rat glomerular endothelial cell (GEN) antibody [immune-mediated thrombotic microangiopathy (ITM)]. Comparable levels of GEN apoptosis were detected in C+ animals in both models. CVF administration reduced GEN apoptosis by 10- to 12-fold. GEN apoptosis was C5b-9 dependent because PVG C6- rats were protected from GEN loss. Furthermore, functional inhibition of the cell surface complement regulatory protein CD59 by renal perfusion with anti-CD59 antibody in ITM resulted in a 3.5-fold increase in GEN apoptosis. Last, in Con A GN, abrogation of GEN apoptosis preserved endothelial integrity and renal function. This study demonstrates the specific role of C5b-9 in the induction of GEN apoptosis in experimental inflammatory GN, a finding with implications for diseases associated with the presence of antiendothelial cell antibodies.