Autoantigens are translocated into small apoptotic bodies during early stages of apoptosis
Autoantigens are translocated into small apoptotic bodies during early stages of apoptosis
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DOI：
10.1038/sj.cdd.4402239
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发表时间：
2008-01-01
影响因子：
12.4
通讯作者：
Lorenz, H-M
中科院分区：
文献类型：
--
作者：
Schiller, M.;Bekeredjian-Ding, I.;Lorenz, H-M
细胞凋亡的失调或细胞凋亡物质的无效清除被怀疑与系统性红斑狼疮的发病机制有关。凋亡小体 (AB) 等亚细胞片段已被认为是细胞间通讯和免疫功能的调节剂。在这种情况下，我们一直对核抗原和细胞质抗原是否重新定位到 AB 感兴趣。在本研究中，我们鉴定了从凋亡淋巴母细胞中分离出的 AB。我们在 AB 中发现了接头组蛋白（组蛋白 1）和核心组蛋白（组蛋白 2A、组蛋白 2B、组蛋白 3、组蛋白 4）的积累。此外，它们还含有 DNA、RNA 和核糖核蛋白 La/SSB。 AB 中排除了细胞色素 c、HSP 70、抑制素、p53、核基质抗原或核纤层蛋白 B 等蛋白质。 AB 的含量与从活细胞分离的膜微粒中观察到的不同。 AB 的形成发生在细胞凋亡早期。这是在检测到 DNA 降解或磷脂酰丝氨酸暴露之前观察到的。 AB 被单核细胞衍生的吞噬细胞吞噬。这些发现表明，免疫原性分子主动转移到 AB 中，然后被环境吞噬细胞快速吞噬。在自身免疫性疾病中，AB 清除或 AB 形成的缺陷可能会导致自身免疫的发生。
A dysregulation of apoptosis or an ineffective clearance of apoptotic material is suspected to be involved in the pathogenesis of systemic lupus erythematodes. Subcellular fragments such as apoptotic bodies (ABs) have been recognized as modulators of intercellular communication and immune function. In this context, we have been interested whether nuclear and cytoplasmic antigens are relocated into ABs. In the present study, we characterized ABs isolated from apoptozing lymphoblasts. We found an accumulation of the linker-histone (histone 1) as well as the core-histones (histone 2A, histone 2B, histone 3, histone 4) in ABs. Further, they contained DNA, RNA and the ribonuclear protein La/SSB. Proteins such as cytochrome c, HSP 70, prohibitin, p53, nuclear matrix antigen or lamin B were excluded from ABs. The content of ABs differed from that observed in membrane microparticles isolated from viable cells. Formation of ABs occurred early during apoptosis. It was observed before DNA-degradation or phosphatidylserine exposure was detected. ABs were engulfed by monocyte-derived phagocytes. These findings suggest that immunogenic molecules are actively translocated into ABs followed by a rapid engulfment of the latter by environmental phagocytes. In autoimmune diseases, a defect in the clearance of ABs or AB formation may contribute to the development of autoimmunity.