[Emerging roles of phospholipase A2s in mast cell biology]

Abstract

Tissue-resident mast cells are derived from circulating committed progenitors, which are originated from pluripotent hematopoietic stem cells in bone marrow. These progenitors migrate into extravascular tissues, where they undergo differentiation and maturation into tissue-specific mast cell phenotypes. When activated by antigen or microenvironmental factors, mast cells release various biologically active products, including pre-formed mediators stored in secretory granules, de novo synthesized lipid mediators, and newly transcribed cytokines and chemokines, thereby promoting anaphylactic inflammation as well as other acute and chronic inflammatory diseases. Here, I will highlight the newest understanding of the phospholipase A2 (PLA2)-driven lipid networks in the maturation and effector functions of mast cells and attendant allergic responses. Group III secreted PLA2, the sole mammalian homolog of the potent extrinsic anaphylaxis inducer bee venom PLA2, regulates mast cell maturation through the paracrine prostaglandin D2 (PGD2) circuit. While cytosolic PLA2α is essential for the generation of PGD2 and leukotriene C4 by mast cells, it is also functionally coupled, through the arachidonic acid transfer mechanism, with PGE2 synthase in stromal fibroblasts to provide anti-anaphylactic PGE2. In addition, the roles of two particular mast cell maturation-responsible genes, NDRG1 and NLRP3, in mast cells will be discussed.