Taketomi Yoshitaka, Murakami Makoto
Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science.
Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo.
Yakugaku Zasshi. 2017;137(5):503-515. doi: 10.1248/yakushi.16-00239-2.
Mast cells originate from hematopoietic stem cells and undergo terminal maturation in the extravascular tissues, in which they are ultimately resident. Mast maturation, phenotype, and function are dictated by the local microenvironment, which has a significant influence on the ability of mast cells to recognize and respond to stimuli. Activation of mast cells can lead to the release of three distinct classes of mediators, including preformed mediators stored in secretory granules, newly transcribed cytokines and chemokines, and de novo-synthesized bioactive lipid mediators. It is currently recognized that bioactive lipids such as arachidonic acid metabolites (prostaglandins and leukotrienes) released from mast cells modulate innate and adaptive immune responses both directly and indirectly through communication with other microenvironmental immune cells or stroma cells. Moreover, mast cells express a variety of lipid receptors and, if activated by bioactive lipids such as arachidonic acid, ω3 fatty acids, lysophospholipids, and their metabolites, can alter the release and production of other mediators including histamine, cytokines, and chemokines, and thereby alter homeostatic or pathophysiological responses. This review focuses on newly identified functional aspects of bioactive lipids with regard to their immune regulation and functional outcomes in both homeostasis and allergic disease.
肥大细胞起源于造血干细胞,并在血管外组织中经历终末成熟,最终定居于此。肥大细胞的成熟、表型和功能由局部微环境决定,局部微环境对肥大细胞识别和响应刺激的能力有显著影响。肥大细胞的激活可导致三类不同介质的释放,包括储存在分泌颗粒中的预形成介质、新转录的细胞因子和趋化因子,以及从头合成的生物活性脂质介质。目前已知,肥大细胞释放的生物活性脂质,如花生四烯酸代谢产物(前列腺素和白三烯),通过与其他微环境免疫细胞或基质细胞的通讯,直接和间接调节固有免疫和适应性免疫反应。此外,肥大细胞表达多种脂质受体,如果被花生四烯酸、ω3脂肪酸、溶血磷脂及其代谢产物等生物活性脂质激活,可改变包括组胺、细胞因子和趋化因子在内的其他介质的释放和产生,从而改变稳态或病理生理反应。本综述重点关注生物活性脂质在免疫调节以及稳态和过敏性疾病中的功能结果方面新发现的功能特性。