The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway
The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway
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DOI：
10.1093/embo-reports/kvf198
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发表时间：
2002-10-01
期刊：
影响因子：
7.7
通讯作者：
Rubartelli, A
中科院分区：
文献类型：
--
作者：
Gardella, S;Andrei, C;Rubartelli, A
HMGB1 是一种非组蛋白核因子，在细胞外充当延迟内毒素致死性的介质，这就提出了核蛋白如何到达细胞外空间的问题。我们发现单核细胞的激活导致 HMGB1 从细胞核重新分布到细胞质细胞器，从而显示出内溶酶体的超微结构特征。 HMGB1 分泌是由触发溶酶体胞吐作用的刺激诱导的。炎症早期介质白介素 (IL)-1β 也由单核细胞通过涉及分泌性溶酶体胞吐作用的非经典途径分泌。然而，根据其各自早期和晚期炎症因子的作用，IL-1β和HMGB1在不同时间对不同刺激做出反应：IL-1β分泌较早由ATP诱导，在激活后不久由单核细胞自分泌释放； HMGB1 的分泌是由随后在炎症部位产生的溶血磷脂酰胆碱触发的。因此，在单核细胞中，非经典分泌可以通过至少部分不同的囊泡区室发生。
HMGB1, a non-histone nuclear factor, acts extracellularly as a mediator of delayed endotoxin lethality, which raises the question of how a nuclear protein can reach the extracellular space. We show that activation of monocytes results in the redistribution of HMGB1 from the nucleus to cytoplasmic organelles, which display ultrastructural features of endolysosomes. HMGB1 secretion is induced by stimuli triggering lysosome exocytosis. The early mediator of inflammation interleukin (IL)-1beta is also secreted by monocytes through a non-classical pathway involving exocytosis of secretory lysosomes. However, in keeping with their respective role of early and late inflammatory factors, IL-1beta and HMGB1 respond at different times to different stimuli: IL-1beta secretion is induced earlier by ATP, autocrinally released by monocytes soon after activation; HMGB1 secretion is triggered by lysophosphatidylcholine, generated later in the inflammation site. Thus, in monocytes, non-classical secretion can occur through vescicle compartments that are at least partially distinct.