Basu S, Binder R J, Suto R, Anderson K M, Srivastava P K
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, MC1601, Farmington, CT 06030-1601, USA.
Int Immunol. 2000 Nov;12(11):1539-46. doi: 10.1093/intimm/12.11.1539.
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-kappa B 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.
树突状细胞（DC）是先天性和适应性免疫反应的关键组成部分。激活DC的内源性信号的身份是一个关键且尚未解决的问题。我们在此报告，热休克蛋白（HSP）作为哺乳动物中最丰富且保守的分子，构成了这样一种内部信号。坏死而非凋亡性细胞死亡会导致HSP gp96、钙网蛋白、hsp90和hsp70的释放。HSP刺激巨噬细胞分泌细胞因子，并诱导DC上抗原呈递分子和共刺激分子的表达。HSP gp96和hsp70的作用有所不同，且各自诱导部分而非全部分子。HSP通过高度保守的NF-κB途径与这些抗原呈递细胞相互作用。由于HSP是细胞内的、丰富且可溶的，它们在细胞外环境中的存在以及由此导致的抗原呈递细胞（APC）的激活构成了对细胞死亡作出反应的极佳机制。由于HSP从细菌到哺乳动物都是保守的，HSP激活APC的能力为应对内部和外部刺激提供了一种统一机制。
