Utrecht Institute for Pharmaceutical Sciences, Universiteitsweg 99, Utrecht, the Netherlands.
Curr Pharm Des. 2012;18(16):2278-89. doi: 10.2174/138161212800166059.
Mast cells are increasingly recognized as critical players in elicitation and maintenance of different inflammatory related disorders, like allergy, autoimmune diseases and cancer. Mast cells maturate within the tissue and are able to adapt to microenvironmental changes. Together with the ability to produce multiple pro- and anti-inflammatory mediators upon activation, mast cells are highly capable of exerting immunomodulatory functions. Cross-linking of receptor bound IgE is the best known mechanism of antigen-specific mast cell activation. In this review we focus on a different route of activation, via immunoglobulin free light chains (FLCs). Here, we describe current knowledge and concepts on FLCs based on preclinical models and data on human subjects, after briefly recapitulating early research findings on FLCs. Furthermore, because FLC research mainly focuses on mast cells, several mast cell mediated pathologies and mouse models for mast cell research will be discussed. Whether targeting of mast cells is beneficial for the treatment of specific disorders has to be addressed in future studies. Specific inhibition of FLC-mediated mast cell activation may be an interesting avenue to treat chronic inflammatory diseases.
肥大细胞越来越被认为是引发和维持不同炎症相关疾病（如过敏、自身免疫性疾病和癌症）的关键因素。肥大细胞在组织中成熟，并能够适应微环境变化。肥大细胞在激活后能够产生多种促炎和抗炎介质，因此具有很强的免疫调节功能。受体结合 IgE 的交联是抗原特异性肥大细胞激活的最佳已知机制。在这篇综述中，我们专注于另一种激活途径，即通过免疫球蛋白游离轻链（FLC）。在这里，我们根据临床前模型和人类受试者的数据，描述了目前关于 FLC 的知识和概念，简要回顾了早期关于 FLC 的研究结果。此外，由于 FLC 研究主要集中在肥大细胞上，因此还将讨论几种肥大细胞介导的病理学和用于肥大细胞研究的小鼠模型。在未来的研究中，需要确定针对肥大细胞的靶向治疗是否对特定疾病有益。特异性抑制 FLC 介导的肥大细胞激活可能是治疗慢性炎症性疾病的一个有趣途径。
