Role of apoptosis in autoimmunity
Role of apoptosis in autoimmunity
复制标题
DOI：
10.1023/a:1009692902805
复制
发表时间：
2000-11-01
期刊：
影响因子：
7.2
通讯作者：
Kalden, JR
中科院分区：
文献类型：
--
作者：
Lorenz, HM;Herrmann, M;Kalden, JR
细胞凋亡是一种生理形式的细胞死亡，需要确保细胞分裂的速率与多细胞生物体中细胞死亡的速率平衡。细胞凋亡的失调与多种疾病的发病机制有关：癌症、神经变性、自身免疫、心脏病等。在这篇综述中，我们收集的论点支持一个假说，失调的细胞凋亡导致发展的自身免疫系统性红斑狼疮（SLE）。这一观点得到了已知的自身抗原在凋亡性大疱中的发生，尽管有最佳的细胞因子刺激，但淋巴母细胞凋亡率增加的体外发现，以及SLE吞噬细胞对凋亡小体的体外清除缺陷的支持。此外，我们和其他人可以产生组蛋白特异性淋巴细胞系的细胞激活后，与自体凋亡材料。这些淋巴细胞可以刺激自体B淋巴细胞产生抗dsDNA抗体，这是SLE的诊断标志。最后，抗磷脂（如磷脂酰丝氨酸）的抗体通常与系统性自身免疫病（如SLE等）相关。磷脂酰丝氨酸作为程序性细胞死亡的早期信号暴露于凋亡细胞上，并作为凋亡细胞的吞噬细胞识别分子。免疫复合物的形成和在组织中的沉积可能导致器官损伤和疾病。本综述将详细讨论这种情况。
Apoptosis is a physiological form of cell death required to ensure that the rate of cell division is balanced by the rate of cell death in multicellular organisms. Dysregulation of apoptosis is associated with the pathogenesis of a wide array of diseases: cancer, neurodegeneration, autoimmunity, heart disease and others. In this review we collect arguments supporting a hypothesis of a dysregulated apoptosis leading to development of autoimmunity like systemic lupus erythematosus (SLE). This notion is supported by occurence of known autoantigens in apoptotic blebs, in vitro findings of an increased rate of apoptotic lymphoblasts despite optimal cytokine stimulation combined with a defective in vitro clearance of apoptotic bodies by SLE phagocytes. Moreover, we and others could generate histone-specific lymphocytic cell lines from cells after activation with autologous apoptotic material. These lymphocytes could stimulate autologous B-lymphocytes to produce of anti-dsDNA antibodies, a diagnostic hallmark for SLE. Finally, antibodies against phospholipids like phosphatidylserine are often associated with systemic autoimmunopathies like SLE and others. Phosphatidylserine is exposed on apoptotic cells as early sign of programmed cell death and serves as phagocyte recognition molecule for apoptotic cells. Formation of immune complexes and deposition in tissues might lead to organ damage and disease. This scenario will be discussed in this review in detail.