Mast cell maturation is driven via a group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis

  • Nat Immunol. 2013 Jun;14(6):554-63. doi: 10.1038/ni.2586.
Yoshitaka Taketomi  1 ,  Noriko Ueno ,  Takumi Kojima ,  Hiroyasu Sato ,  Remi Murase ,  Kei Yamamoto ,  Satoshi Tanaka ,  Mariko Sakanaka ,  Masanori Nakamura ,  Yasumasa Nishito ,  Momoko Kawana ,  Naotomo Kambe ,  Kazutaka Ikeda ,  Ryo Taguchi ,  Satoshi Nakamizo ,  Kenji Kabashima ,  Michael H Gelb ,  Makoto Arita ,  Takehiko Yokomizo ,  Motonao Nakamura ,  Kikuko Watanabe ,  Hiroyuki Hirai ,  Masataka Nakamura ,  Yoshimichi Okayama ,  Chisei Ra ,  Kosuke Aritake ,  Yoshihiro Urade ,  Kazushi Morimoto ,  Yukihiko Sugimoto ,  Takao Shimizu ,  Shuh Narumiya ,  Shuntaro Hara ,  Makoto Murakami
Affiliations
  • 1. Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
PMID: 23624557 DOI: 10.1038/ni.2586
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.