CYCLOOXYGENASE-2-DEPENDENT DELAYED PROSTAGLANDIN D-2 GENERATION IS INITIATED BY NERVE GROWTH-FACTOR IN RAT PERITONEAL MAST-CELLS - ITS AUGMENTATION BY EXTRACELLULAR TYPE-II SECRETORY PHOSPHOLIPASE A(2)

When rat serosal connective tissue mast cells (CTMC) were stimulated w ith nerve growth factor (NGF), the immediate prostaglandin D-2 (PGD(2) ) generation was followed by delayed PGD(2) generation that occurred b etween 2 and 24 h, reaching levels as high as 50 ng and 260 ng/10(6) c ells in the absence or presence of lysophosphatidylserine (lysoPS), re spectively. This delayed PGD(2) generation was accompanied by de novo induction of cyclooxygenase (COX)-2, with NCF and lysoPS acting as ind ucer and enhancer, respectively. COX-2 induction and the attendant del ayed PGD(2) generation in CTMC were modestly induced by c-kit ligand, but not by Fc epsilon RI cross-linking. This indicated that the stimul us specificity differed from that observed in the immediate phase, in which NGF, c-kif ligand, and Fc epsilon RI cross-linking, either in co mbination with each other or with lysoPS as a cofactor, elicited compa rable levels of PGD(2) generation within 10 min, reaching 10 to 20 ng/ 10(6) cells, Addition of type II secretory phospholipase A(2) (sPLA(2) ), a PLA(2) isoform that is detected in mu g/ml levels in inflammatory exudates, to NGF-stimulated CTMC significantly augmented delayed, but not immediate, PGD(2) generation, and this augmentative effect was me diated in part by the enhancement of COX-2 expression by sPLA(2). Thes e results suggest that CTMC have the capacity to produce PGD(2) over a prolonged period in the presence of tissue-derived cytokines and sPLA (2) in a COX-2-dependent manner.