The expression of cyclooxygenase and the production of prostaglandin E2 in neutrophils after burn injury and infection.

Abstract

Recent studies have demonstrated that neutrophils have the capacity to produce a variety of cytokines after stimulation. The synthesis and release of prostaglandin E2 (PGE2) via the cyclooxygenase (COX) pathway has been reported to occur in activated neutrophils. In the present study, we sought to determine the status of COX protein synthesis and PGE2 production in murine neutrophils after burn injury. The effect of burn injury on neutrophil COX and PGE2 response to infection or lipopolysaccharide (LPS) was also examined. Peritoneal neutrophils were obtained from BDF1 mice at 4, 18, 24, and 36 hours after a 15% TBSA full-thickness scald burn or sham burn. We found that neutrophils from healthy mice express a low level of COX-2 protein. Neutrophil COX-2 protein expression in burn animals was significantly increased at 4 hours and dramatically decreased at 36 hours after burn injury. Animals 36 hours after burn and topically infected with Pseudomonas Aeruginosa had neutrophil COX-2 expression almost identical to burn injury only. Neutrophils harvested from healthy mice cocultured with LPS (1 microg/ml) had a marked induction of COX-2 protein. Neutrophils 24 hours after burn were unresponsive to LPS-stimulated COX-2 enhancement. COX-1 protein was strongly expressed constitutively and not affected further by burn injury or LPS. The production of PGE2 corresponded with the changes in COX-2 expression for all groups of mice. Our data suggested that neutrophils express both COX-1 and COX-2 and produce PGE2. The effects of burn injury on neutrophil COX-2 protein synthesis and PGE2 production suggest that after burn there is a time-dependent response. Insights into not only the global cellular response to injury and infection but also temporal nature of the response are important in the development of the therapeutic treatment strategies for burn patients.