Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway
Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway
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DOI：
10.1093/intimm/12.11.1539
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发表时间：
2000-11-01
影响因子：
4.4
通讯作者：
Srivastava, PK
中科院分区：
文献类型：
--
作者：
Basu, S;Binder, RJ;Srivastava, PK
树突状细胞(DC)是天然免疫和获得性免疫反应的重要组成部分，激活DC的内源性信号的识别是一个关键且尚未解决的问题。我们在这里报道，热休克蛋白(HSP)是哺乳动物中含量最丰富、最保守的分子，它构成了这样的内部信号。HSP刺激巨噬细胞分泌细胞因子，诱导DC上抗原提呈分子和共刺激分子表达，HSP gp96和HSP70的作用不同，各自诱导部分而不是全部分子的表达。热休克蛋白通过高度保守的NF-kappaB途径与这些抗原提呈细胞相互作用。由于热休克蛋白是细胞内的、丰富的和可溶的，它们存在于细胞外环境中，从而激活抗原提呈细胞(APC)，构成了一种很好的细胞死亡应答机制。由于HSP从细菌到哺乳动物都是保守的，HSP激活APC的能力为反应内外刺激提供了一种统一的机制。
Dendritic cells (DC) are key components of innate and adaptive immune responses, The identity of endogenous signals that activate DC is a crucial and unresolved question. We report here that heat shock proteins (HSP), the most abundant and conserved mammalian molecules, constitute such an internal signal. Necrotic but not apoptotic cell death leads to release of HSP gp96, calreticulin, hsp90 and hsp70, HSP stimulate macrophages to secrete cytokines, and induce expression of antigen-presenting and co-stimulatory molecules on the DC, The HSP gp96 and hsp70 act differentially, and each induces some but not all molecules. HSP interact with these antigen-presenting cells through the highly conserved NF-kappaB pathway. As HSP are intracellular, abundant and soluble, their presence in the extra-cellular milieu and the consequent activation of antigen-presenting cells (APC) constitutes an excellent mechanism for response to cell death. As HSP are conserved from bacteria to mammals, the ability of HSP to activate APC provides a unified mechanism for response to internal and external stimuli.