title: Cyclooxygenase-2-dependent delayed prostaglandin D2 generation is initiated by nerve growth factor in rat peritoneal mast cells: its augmentation by extracellular type II secretory phospholipase A2.
abstract: When rat serosal connective tissue mast cells (CTMC) were stimulated with nerve growth factor (NGF), the immediate prostaglandin D2 (PGD2) generation was followed by delayed PGD2 generation that occurred between 2 and 24 h, reaching levels as high as 50 ng and 260 ng/10(6) cells in the absence or presence of lysophosphatidylserine (lysoPS), respectively. This delayed PGD2 generation was accompanied by de novo induction of cyclooxygenase (COX)-2, with NGF and lysoPS acting as inducer and enhancer, respectively. COX-2 induction and the attendant delayed PGD2 generation in CTMC were modestly induced by c-kit ligand, but not by Fc epsilonRI cross-linking. This indicated that the stimulus specificity differed from that observed in the immediate phase, in which NGF, c-kit ligand, and Fc epsilonRI cross-linking, either in combination with each other or with lysoPS as a cofactor, elicited comparable levels of PGD2 generation within 10 min, reaching 10 to 20 ng/10(6) cells. Addition of type II secretory phospholipase A2 (sPLA2), a PLA2 isoform that is detected in microg/ml levels in inflammatory exudates, to NGF-stimulated CTMC significantly augmented delayed, but not immediate, PGD2 generation, and this augmentative effect was mediated in part by the enhancement of COX-2 expression by sPLA2. These results suggest that CTMC have the capacity to produce PGD2 over a prolonged period in the presence of tissue-derived cytokines and sPLA2 in a COX-2-dependent manner.
authors.affiliation: Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Murakami
authors.forename: K
authors.initials: K
authors.lastname: Tada
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: I
authors.initials: I
authors.lastname: Kudo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D007527:Isoenzymes / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010529:Peritoneal Cavity; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007527:Isoenzymes; D009414:Nerve Growth Factors; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D015230:Prostaglandin D2