Department of Internal Medicine V, Division of Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Autoimmunity. 2013 Aug;46(5):342-6. doi: 10.3109/08916934.2012.750302. Epub 2013 Jan 17.
High mobility group box protein B1 (HMGB1), a nuclear protein reportedly involved in the structural organisation of DNA, is released from necrotic cells or upon cellular activation. After its release into the extracellular space, HMGB1 serves as a mediator of inflammation. In contrast to necrotic cells, apoptotic ones usually do not release HMGB1. Formation and release of membranous vesicles is a well-known feature of apoptotic cell death. Only recently, subcellular membrane vesicles, such as those released during apoptotic cell death have been identified as immune regulators and as mediators of cell to cell communication. We and others have previously detected nuclear antigens within apoptosis-released membranous vesicles and HMGB1 together with nuclear antigens has been discussed to be a key player in etiology and pathogenesis of autoimmune diseases. On this background, we analysed whether HMGB1 is included in the membranous vesicles generated by apoptosing cells. Employing immune blots we observed abundand amounts of HMGB1 in the fraction of the small membraneous particles isolated from cell culture supernatants and conclude that HMGB1 is translocated into vesicles generated during apoptosis.
高迁移率族蛋白 B1(HMGB1)是一种核蛋白,据报道参与 DNA 的结构组织,它从坏死细胞或细胞活化时释放出来。在释放到细胞外空间后,HMGB1 作为炎症的介质。与坏死细胞不同,凋亡细胞通常不会释放 HMGB1。膜囊泡的形成和释放是凋亡细胞死亡的一个众所周知的特征。直到最近,亚细胞膜囊泡,如在凋亡细胞死亡期间释放的那些,才被确定为免疫调节剂和细胞间通讯的介质。我们和其他人以前已经在凋亡释放的膜囊泡内检测到核抗原,并且 HMGB1 与核抗原一起被认为是自身免疫性疾病病因和发病机制的关键因素。在此背景下,我们分析了 HMGB1 是否包含在凋亡细胞产生的膜性囊泡中。通过免疫印迹,我们观察到从小型膜性颗粒分离的细胞培养上清液部分中 HMGB1 的含量丰富,并得出结论,HMGB1 被转移到凋亡过程中产生的囊泡中。