Morita H, Isobe K, Cai Z, Miyazaki T, Matsumoto Y, Shinzato T, Yoshikai Y, Kimata K, Maeda K
Department of Internal Medicine, Branch Hospital of Nagoya University, School of Medicine, Japan.
Nephron. 1996;73(2):293-8. doi: 10.1159/000189054.
Injection of anti-Thy-1 antibody into a rat induces immediate glomerular cell death and subsequent development of glomerulonephritis. Whether the immediate cell death in this model is apoptotic has yet to be determined. Recent in vivo studies on thymocyte death have elucidated that the Thy-1 molecule can activate intracellular signaling for apoptosis. This observation prompted us to re-examine whether stimulation with anti-Thy-1 antibody can provoke apoptosis in the rat glomerulus. We found that anti-Thy-1 antibody could induce laddered DNA fragmentation of isolated glomeruli and mesangial cells in culture, definite biochemical evidence for random double-stranded breaks through apoptosis. Such DNA laddering was also demonstrated in the isolated glomeruli of rats that had been infused with anti-Thy-1 antibody several hours before. Furthermore, the terminal deoxynucleotidyl-transferase-mediated oligonucleotide nick end labeling technique stained a cell in the mesangium. Although apoptosis may be considered a candidate mechanism mediating resolution of hypercellularity in the anti-Thy-1 model, we propose that it is also involved in the immediate cell death in this model.
向大鼠体内注射抗Thy-1抗体可导致肾小球细胞立即死亡，并随后引发肾小球肾炎。该模型中细胞的立即死亡是否为凋亡性死亡尚未确定。最近关于胸腺细胞死亡的体内研究表明，Thy-1分子可激活细胞内凋亡信号。这一观察结果促使我们重新研究抗Thy-1抗体刺激是否能引发大鼠肾小球凋亡。我们发现抗Thy-1抗体可诱导培养的分离肾小球和系膜细胞出现DNA梯状条带，这是通过凋亡产生随机双链断裂的确切生化证据。在数小时前已注入抗Thy-1抗体的大鼠分离肾小球中也证实了这种DNA梯状条带。此外，末端脱氧核苷酸转移酶介导的寡核苷酸缺口末端标记技术标记了系膜中的一个细胞。虽然凋亡可能被认为是抗Thy-1模型中介导细胞增多症消退的候选机制，但我们认为它也参与了该模型中的细胞立即死亡。
