Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, Stockholm, Sweden.
J Innate Immun. 2011;3(2):142-9. doi: 10.1159/000321933. Epub 2010 Nov 24.
Mast cells are among the first cells of our immune system to encounter exogenous danger. Intracellular receptors such as nucleotide-binding oligomerization domain (Nod) play an important role in responding to invading pathogens. Here, we have investigated the response of human mast cells to the Nod1 ligand M-TriDAP. Human cord blood-derived mast cells (CBMCs) were activated with M-TriDAP alone, or in combination with the Toll-like receptor (TLR) ligands lipopolysaccharide (LPS) and zymosan. Release of pro-inflammatory chemokines and cytokines was measured by ELISA, cytometric bead array and LUMINEX, and degranulation was evaluated by analysis of histamine release. M-TriDAP induced a dose-dependent release of IL-8, MIP-1α, MIP-1β and TNF. In contrast, degranulation could not be observed. When cells were treated with M-TriDAP in combination with the TLR4 agonist LPS, but not with TLR2 agonist zymosan, the secretion of cytokines was augmented. We here present results demonstrating that human CBMCs are stimulated by the Nod1 agonist M-TriDAP alone and in combination with LPS to produce pro-inflammatory cytokines and chemokines. Our results add to the concept that mast cells constitute an important part of our host defense, as they are equipped with several types of important pattern recognition receptors, including TLRs and Nod.
肥大细胞是我们免疫系统中最先接触到外源性危险的细胞之一。细胞内受体，如核苷酸结合寡聚化结构域（Nod），在应对入侵病原体方面发挥着重要作用。在这里，我们研究了人肥大细胞对 Nod1 配体 M-TriDAP 的反应。我们单独用 M-TriDAP 或与 Toll 样受体（TLR）配体脂多糖（LPS）和酵母聚糖联合激活人脐带血来源的肥大细胞（CBMC）。通过 ELISA、细胞因子珠阵列和 LUMINEX 测量促炎趋化因子和细胞因子的释放，通过分析组胺释放评估脱颗粒。M-TriDAP 诱导 IL-8、MIP-1α、MIP-1β 和 TNF 的剂量依赖性释放。相比之下，未观察到脱颗粒。当用 TLR4 激动剂 LPS 而不是 TLR2 激动剂酵母聚糖处理细胞时，细胞因子的分泌增加。我们在此介绍的结果表明，Nod1 激动剂 M-TriDAP 可单独或与 LPS 联合刺激人 CBMC 产生促炎细胞因子和趋化因子。我们的结果增加了肥大细胞构成宿主防御重要组成部分的概念，因为它们配备了几种重要的模式识别受体，包括 TLR 和 Nod。
