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.
Original language | English |
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Pages (from-to) | 554-563 |
Number of pages | 10 |
Journal | Nature Immunology |
Volume | 14 |
Issue number | 6 |
DOIs | |
Publication status | Published - Jun 2013 |
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ASJC Scopus subject areas
- Immunology
Cite this
Mast cell maturation is driven via a group III phospholipase A 2-prostaglandin D2-DP1 receptor paracrine axis. / Taketomi, Yoshitaka; Ueno, Noriko; Kojima, Takumi; Sato, Hiroyasu; Murase, Remi; Yamamoto, Kei; Tanaka, Satoshi; Sakanaka, Mariko; Nakamura, Masanori; Nishito, Yasumasa; Kawana, Momoko; Kambe, Naotomo; Ikeda, Kazutaka; Taguchi, Ryo; Nakamizo, Satoshi; Kabashima, Kenji; Gelb, Michael H.; Arita, Makoto; Yokomizo, Takehiko; Nakamura, Motonao; Watanabe, Kikuko; Hirai, Hiroyuki; Nakamura, Masataka; Okayama, Yoshimichi; Ra, Chisei; Aritake, Kosuke; Urade, Yoshihiro; Morimoto, Kazushi; Sugimoto, Yukihiko; Shimizu, Takao; Narumiya, Shuh; Hara, Shuntaro; Murakami, Makoto.
In: Nature Immunology, Vol. 14, No. 6, 06.2013, p. 554-563.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mast cell maturation is driven via a group III phospholipase A 2-prostaglandin D2-DP1 receptor paracrine axis
AU - Taketomi, Yoshitaka
AU - Ueno, Noriko
AU - Kojima, Takumi
AU - Sato, Hiroyasu
AU - Murase, Remi
AU - Yamamoto, Kei
AU - Tanaka, Satoshi
AU - Sakanaka, Mariko
AU - Nakamura, Masanori
AU - Nishito, Yasumasa
AU - Kawana, Momoko
AU - Kambe, Naotomo
AU - Ikeda, Kazutaka
AU - Taguchi, Ryo
AU - Nakamizo, Satoshi
AU - Kabashima, Kenji
AU - Gelb, Michael H.
AU - Arita, Makoto
AU - Yokomizo, Takehiko
AU - Nakamura, Motonao
AU - Watanabe, Kikuko
AU - Hirai, Hiroyuki
AU - Nakamura, Masataka
AU - Okayama, Yoshimichi
AU - Ra, Chisei
AU - Aritake, Kosuke
AU - Urade, Yoshihiro
AU - Morimoto, Kazushi
AU - Sugimoto, Yukihiko
AU - Shimizu, Takao
AU - Narumiya, Shuh
AU - Hara, Shuntaro
AU - Murakami, Makoto
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84878250182&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878250182&partnerID=8YFLogxK
U2 - 10.1038/ni.2586
DO - 10.1038/ni.2586
M3 - Article
C2 - 23624557
AN - SCOPUS:84878250182
VL - 14
SP - 554
EP - 563
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 6
ER -