1. Mast cell maturation is driven via a group III phospholipase A2-prostaglandin D2–DP1 receptor paracrine axis
- Author
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Masataka Nakamura, Makoto Arita, Masanori Nakamura, Naotomo Kambe, Satoshi Nakamizo, Remi Murase, Hiroyuki Hirai, Kikuko Watanabe, Michael H. Gelb, Momoko Kawana, Yukihiko Sugimoto, Yasumasa Nishito, Kazutaka Ikeda, Yoshitaka Taketomi, Kazushi Morimoto, Ryo Taguchi, Kei Yamamoto, Noriko Ueno, Kosuke Aritake, Satoshi Tanaka, Takehiko Yokomizo, Mariko Sakanaka, Yoshihiro Urade, Kenji Kabashima, Shuh Narumiya, Makoto Murakami, Takao Shimizu, Motonao Nakamura, Hiroyasu Sato, Shuntaro Hara, Chisei Ra, Takumi Kojima, and Yoshimichi Okayama
- Subjects
Mice, 129 Strain ,Blotting, Western ,Receptors, Prostaglandin ,Immunology ,Bone Marrow Cells ,Article ,Mice ,Paracrine signalling ,chemistry.chemical_compound ,Phospholipase A2 ,Microscopy, Electron, Transmission ,Paracrine Communication ,medicine ,Animals ,Humans ,Immunology and Allergy ,Mast Cells ,Receptor ,Cells, Cultured ,Oligonucleotide Array Sequence Analysis ,Mice, Knockout ,biology ,Prostaglandin D2 ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Group III Phospholipases A2 ,Degranulation ,Cell Differentiation ,Fibroblasts ,Mast cell ,Phenotype ,Lipocalins ,Cell biology ,Intramolecular Oxidoreductases ,Mice, Inbred C57BL ,Interleukin 33 ,medicine.anatomical_structure ,chemistry ,biology.protein ,lipids (amino acids, peptides, and proteins) - 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.
- Published
- 2013