Cultured human MCs (hMCs) derived from cord blood were stimulated by either Fc epsilon RI cross-linkage, or by staphylococcal peptidoglycan (PGN), a ligand for Toll-like receptor (TLR)2. Eicosanoids were measured by ELISA, and relevant enzymes and proteins were assessed by western blots.
Unexpectedly, both ligands elicited the generation of PGE2, as well as LTC4 and PGD2. Whereas Fc epsilon RI-dependent activation was far more potent for LTC4 and PGD2 generation, PGN was more potent for PGE2 generation, which occurred with a strikingly delayed kinetics (maximal at 24 h). Both activation stimuli induced the expression of COX-2 and two terminal synthases, mPGES-1 and mPGES-2. Delayed-phase PGE2 generation was completely prevented by NS-398, a selective PGHS-2 inhibitor.
MCs express an inducible system for PGE2 generation, and likely produce different respective profiles of eicosanoids in innate and adaptive immune responses. The inducible COX-2/mPGES system may form a pathogenetic link between MCs and non-allergic diseases in which PGE2 plays a major role.