マスト細胞生物学における脂質代謝ネットワーク

概要

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Tissue-resident mast cells are derived from circulating committed progenitors, which are originated from pluripotential hematopoietic stem cells in bone marrow. These progenitors migrate into extravascular tissues, where they undergo differentiation and maturation into tissue-specific mature phenotypes. When activated by IgE/antigen, stem cell factor, neuropeptides, or other stimuli, mature mast cells release three classes of biologically active products, including pre-formed mediators stored in secretory granules, newly transcribed cytokines and chemokines, and de novo synthesized lipid mediators. Therefore, these cells have been implicated as major effector cells in acute and chronic inflammatory diseases. In recent years, it has become clear that lipid mediators including arachidonic acid metabolites (prostaglandins and leukotrienes) and lysophospholipid-derived products play crucial roles in mast cell-associated pathology. In this article, we will provide an overview of the roles of various lipid mediators in allergic diseases fueled by studies of their biosynthetic enzymes or receptors. In the latter part, we will make a particular focus on phospholipase A2 enzymes, which are placed at the bottleneck (rate-limiting) step of the lipid mediator-biosynthetic pathways.