title: Mast cell maturation is driven via a group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis.
abstract: Microenvironment-based alterations in phenotypes of mast cells influence the susceptibility to anaphylaxis, yet the mechanisms underlying proper maturation of mast cells toward an anaphylaxis-sensitive phenotype are incompletely understood. Here we report that PLA2G3, a mammalian homolog of anaphylactic bee venom phospholipase A2, regulates this process. PLA2G3 secreted from mast cells is coupled with fibroblastic lipocalin-type PGD2 synthase (L-PGDS) to provide PGD2, which facilitates mast-cell maturation via PGD2 receptor DP1. Mice lacking PLA2G3, L-PGDS or DP1, mast cell-deficient mice reconstituted with PLA2G3-null or DP1-null mast cells, or mast cells cultured with L-PGDS-ablated fibroblasts exhibited impaired maturation and anaphylaxis of mast cells. Thus, we describe a lipid-driven PLA2G3-L-PGDS-DP1 loop that drives mast cell maturation.
authors.affiliation: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Taketomi
authors.forename: Noriko
authors.initials: N
authors.lastname: Ueno
authors.forename: Takumi
authors.initials: T
authors.lastname: Kojima
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sato
authors.forename: Remi
authors.initials: R
authors.lastname: Murase
authors.forename: Kei
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Mariko
authors.initials: M
authors.lastname: Sakanaka
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Nishito
authors.forename: Momoko
authors.initials: M
authors.lastname: Kawana
authors.forename: Naotomo
authors.initials: N
authors.lastname: Kambe
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
authors.forename: Ryo
authors.initials: R
authors.lastname: Taguchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakamizo
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokomizo
authors.forename: Motonao
authors.initials: M
authors.lastname: Nakamura
authors.forename: Kikuko
authors.initials: K
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hirai
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Okayama
authors.forename: Chisei
authors.initials: C
authors.lastname: Ra
authors.forename: Kosuke
authors.initials: K
authors.lastname: Aritake
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.forename: Kazushi
authors.initials: K
authors.lastname: Morimoto
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Hara
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D020869:Gene Expression Profiling; D054520:Group III Phospholipases A2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054834:Lipocalins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D020411:Oligonucleotide Array Sequence Analysis; D019899:Paracrine Communication / Q000235:genetics / Q000276:immunology*; D015230:Prostaglandin D2 / Q000276:immunology* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D054834:Lipocalins; D011982:Receptors, Prostaglandin; C527097:prostanoid D receptor 1, mouse; D054520:Group III Phospholipases A2; C541931:PLA2G3 protein, mouse; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2