Tessarz Anja S, Cerwenka Adelheid
German Cancer Research Center DKFZ, Division of Innate Immunity, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Immunol Lett. 2008 Mar 15;116(2):111-6. doi: 10.1016/j.imlet.2007.11.021. Epub 2007 Dec 26.
DNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter, which couples to multiple receptors expressed on natural killer (NK) cells, monocytes, and neutrophils. Initially, DAP12-mediated signaling was mainly investigated downstream of receptors expressed on NK cells. In myeloid cells, one of the receptors associating with DAP12 is the triggering receptor expressed on myeloid cells (TREM)-1. Since the real nature of TREM-1L(s) is still illusive, TREM-1 biology was so far only studied using agonistic monoclonal antibodies for receptor ligation. Triggering via TREM-1 results in the production of pro-inflammatory cytokines, chemokines, reactive oxygen species (ROS), and leads to rapid degranulation of neutrophilic granules, and phagocytosis. Furthermore, application of a TREM-1/Ig fusion protein in an animal model of experimentally induced sepsis increases survival. It is obvious that targeting components of the TREM-1/DAP12 pathway could be a promising therapeutic strategy for the treatment of inflammatory diseases. Therefore, it is of great importance to get further insight into the signaling cascade downstream of TREM-1. This review summarizes the current understanding of the TREM-1/DAP12 pathway in monocytes and neutrophils.
12千道尔顿DNAX激活蛋白（DAP12）是一种基于免疫受体酪氨酸的激活基序（ITAM）的衔接蛋白，它与自然杀伤（NK）细胞、单核细胞和中性粒细胞上表达的多种受体偶联。最初，DAP12介导的信号传导主要在NK细胞上表达的受体下游进行研究。在髓样细胞中，与DAP12相关的受体之一是髓样细胞触发受体（TREM）-1。由于TREM-1L(s)的真实性质仍然不清楚，到目前为止，TREM-1生物学仅使用用于受体连接的激动性单克隆抗体进行研究。通过TREM-1触发会导致促炎细胞因子、趋化因子、活性氧（ROS）的产生，并导致嗜中性粒细胞颗粒的快速脱颗粒和吞噬作用。此外，在实验性诱导脓毒症的动物模型中应用TREM-1/Ig融合蛋白可提高存活率。显然，靶向TREM-1/DAP12途径的成分可能是治疗炎症性疾病的一种有前景的治疗策略。因此，进一步深入了解TREM-1下游的信号级联非常重要。本综述总结了目前对单核细胞和中性粒细胞中TREM-1/DAP12途径的理解。
