Abstract
Rationale Mast cells (MCs) are effectors of both innate and adaptive immunity. MC activation through Fc epsilon RI results in their generation of leukotriene (LT)C4 through the 5-lipoxygenase/leukotriene C4 synthase (5-LO/LTC4S) pathway, and of prostaglandin (PG)D2 through the cyclooxygenase (COX)/PGD2 synthase pathway. PGE2 is generated by both constitutive and inducible enzymatic systems and serves a key role in cell activation and gene induction; its generation by MCs has not been recognized. Methods 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. Results 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. Conclusions 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.