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

Mast cells play pivotal roles in innate host defenses against venom. Activated mast cells release large amounts of prostaglandin D2 (PGD2). However, the role of PGD2 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 PGD2 may enhance host defense against BV and save lives by inhibiting BV absorption into circulation.