Nucleosomes induce lymphocyte necrosis
Nucleosomes induce lymphocyte necrosis
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DOI：
10.1002/eji.200323703
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发表时间：
2003-07-01
影响因子：
5.4
通讯作者：
Rammensee, HG
中科院分区：
文献类型：
--
作者：
Decker, P;Wolburg, H;Rammensee, HG
核小体是系统性红斑狼疮的主要自身抗原。在狼疮患者和狼疮小鼠中都发现了这些循环复合体。已经提出存在一种潜在的无处不在的核小体特异性细胞表面受体。然而，这种受体的性质和作用都还没有确定。此外，受体-核小体相互作用对靶细胞的影响到目前为止还没有详细的研究。我们在这里表明，纯化的核小体在体外以剂量和时间依赖的方式诱导正常和狼疮淋巴细胞的细胞死亡，而人树突状细胞相对耐受。最重要的是，核小体诱导的细胞死亡是原发的坏死。此外，核小体先用脱氧核糖核酸酶I、蛋白水解酶K或用特定的单抗处理可消除坏死。最后，与缓冲液注射的小鼠相比，静脉注射纯化的核小体导致脾细胞数量减少，这表明循环中的核小体在体内的表现可能类似。综上所述，这是第一份表明核小体能够导致坏死的报告，这反过来可能导致疾病的放大循环，导致在狼疮患者中观察到的炎症。
Nucleosomes are major autoantigens in systemic lupus erythematosus. These are found as circulating complexes in both lupus patients and lupus mice. The existence of a potential ubiquitous cell surface receptor specific for nucleosomes has been suggested. However, neither the nature nor the role of this receptor has been identified. Moreover, the consequence of receptor-nucleosome interaction on the target cell has not been studied in detail so far. We show here that purified nucleosomes induce cell death of normal and lupus lymphocytes ex vivo in a dose- and time-dependent manner whereas human dendritic cells were relatively resistant. Most importantly, nucleosome-induced cell death is primary necrosis. Moreover, necrosis could be abolished when nucleosomes; were first treated with deoxyribonuclease I, proteinase K or with a specific monoclonal antibody. Finally, intravenous injections of purified nucleosomes result in a reduced spleen cell number compared to buffer-injected mice, indicating that circulating nucleosomes may behave similarly in vivo. Taken together, this is the first report indicating that nucleosomes are able to induce necrosis, which in turn could result in an amplification loop of the disease causing the inflammation observed in lupus patients.