Effects of group III phospholipase A2 deficiency in mast cells on fibroblast-directed maturation of mast cells in vitro. Mus musculus

Microenvironment-based alterations in mast cell phenotypes 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- or DP1-null mast cells, or mast cells cocultured with L-PGDS-ablated fibroblasts exhibited impaired mast cell maturation and anaphylaxis. Thus, we describe a lipid-driven PLA2G3-L-PGDS-DP1 loop that drives mast cell maturation. Overall design: Model, in vitro mast cell maturation; Cells, bone marrow-derived mast cells (BMMCs) cocultured with Swiss 3T3 fibroblasts; Condition, 4 condition experiments: BMMCs cocultured with (mature) versus without (immature) fibroblasts, Pla2g3 knockout (–/–) versus Pla2g3 wild-type (+/+); Samples, 3 replicates of Pla2g3+/+ BMMCs, 4 replicates of Pla2g3–/– BMMCs, 4 replicates of Pla2g3+/+ cocultuzred BMMCs, 3 replicates of Pla2g3–/– cocultured BMMCs