Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Adv Exp Med Biol. 2012;738:144-52. doi: 10.1007/978-1-4614-1680-7_9.
Multicellular organisms have developed ways to recognize potentially life-threatening events (danger signals). Classically, danger signals have been defined as exogenous, pathogen-associated molecular patterns (PAMPs) such as bacterial cell wall components (e.g., lipopolysaccharide and peptideglycan) or viral DNA/RNA. PAMPs interact with dedicated receptors on immune cells, so-called pattern recognition receptors (PRRs) and activate immune systems. A well-known family of PRRs is the toll-like receptors (TLRs) in which each member recognizes a specific set of PAMPs. However, not only exogenous pathogens but also several endogenous molecules released from necrotic cells (damaged self) also activate immune systems. These endogenous adjuvants are called damage-associated molecular patterns (DAMPs). It has been reported that high-mobility group box 1 protein (HMGB1), uric acid, heat shock proteins (HSPs) and nucleotides act as endogenous adjuvants. DAMPs are recognized by specific receptors (danger receptors) expressed mainly on antigen-presenting cells such as dendritic cells and macrophages and induce cell maturation and the production of inflammatory cytokines by activating the NF-kB pathway. In this chapter, we will review danger signals released from necrotic cells and its recognition receptors.
多细胞生物已经发展出识别潜在危及生命事件（危险信号）的方法。传统上，危险信号被定义为外源性、与病原体相关的分子模式（PAMPs），例如细菌细胞壁成分（例如，脂多糖和肽聚糖）或病毒 DNA/RNA。PAMPs 与免疫细胞上专门的受体（称为模式识别受体（PRRs））相互作用，从而激活免疫系统。PRRs 中一个著名的家族是 Toll 样受体（TLRs），其中每个成员识别特定的 PAMP 集。然而，不仅外源性病原体，而且从坏死细胞（受损自身）释放的几种内源性分子也会激活免疫系统。这些内源性佐剂被称为损伤相关分子模式（DAMPs）。据报道，高迁移率族蛋白 B1 蛋白（HMGB1）、尿酸、热休克蛋白（HSPs）和核苷酸作为内源性佐剂发挥作用。DAMPs 通过激活 NF-kB 途径识别主要在抗原呈递细胞（如树突状细胞和巨噬细胞）上表达的特定受体（危险受体），从而诱导细胞成熟和炎症细胞因子的产生。在本章中，我们将回顾坏死细胞释放的危险信号及其识别受体。
