Crystal‐induced neutrophil activation: VIII. Immediate production of prostaglandin E₂ mediated by constitutive cyclooxygenase 2 in human neutrophils stimulated by urate crystals

OBJECTIVE: To evaluate the impact of monosodium urate monohydrate (MSUM) crystals on the synthesis of prostaglandin E(2) (PGE(2)) by human neutrophils, and to examine some of the mechanisms underlying these responses. METHODS: The amount of PGE(2) released in the supernatants of stimulated human neutrophils was evaluated by enzyme immunoassay, and expression of cyclooxygenase 2 (COX-2) was monitored by immunoblot on cell lysates, as well as by cytofluorometry of buffy-coat cells. RESULTS: We observed that MSUM crystals rapidly stimulated the synthesis of PGE(2), with levels peaking at 1 hour. This response was decreased by NS-398, a specific inhibitor of COX-2. We also detected a constitutive expression of COX-2 in unstimulated and unprimed neutrophils. This rapid COX-2-dependent PGE(2) accumulation was independent of translation and transcription. We also observed that piceatannol, but not colchicine, blocked the synthesis of PGE(2) stimulated by MSUM crystals. CONCLUSION: These results show that the interaction of MSUM crystals with human neutrophils stimulates a significant synthesis of PGE(2) mediated by constitutively expressed COX-2. The results of this study emphasize the potential importance of the neutrophil as a source of PGE(2), which may modulate, positively or negatively, the inflammatory response.