Mast cell-derived prostaglandin D 2 limits the subcutaneous absorption of honey bee venom in mice

Author:

Fujiwara Yuki1,Nakamura Tatsuro1,Maehara Toko1,Hayashi Akane1,Aritake Kosuke2,Murata Takahisa1ORCID

Affiliation:

1. Laboratory of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan

2. Laboratory of Chemical Pharmacology, Daiichi University of Pharmacy, Fukuoka 815-8511, Japan

Abstract

Mast cells play pivotal roles in innate host defenses against venom. Activated mast cells release large amounts of prostaglandin D 2 (PGD 2 ). However, the role of PGD 2 in such host defense remains unclear. We found that c-kit-dependent and c-kit-independent mast cell–specific hematopoietic prostaglandin D synthase ( H-pgds ) deficiency significantly exacerbated honey bee venom (BV)–induced hypothermia and increased mortality rates in mice. BV absorption via postcapillary venules in the skin was accelerated upon endothelial barrier disruption resulting in increased plasma venom concentrations. These results suggest that mast cell–derived PGD 2 may enhance host defense against BV and save lives by inhibiting BV absorption into circulation.

Funder

MEXT | Japan Society for the Promotion of Science

Asahi Group | Asahi Group Foundation

Terumo Life Science Foundation

Research Support Program, SEKISUI CHEMICAL CO., LTD.

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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