Thromboxane synthesis is increased by upregulation of cytosolic phospholipase A2 and cyclooxygenase-2 in peripheral polymorphonuclear leukocytes during bacterial infection in childhood

Abstract

Prostaglandins (PGs) and thromboxane (TX) are important mediators of inflammation. Recent studies revealed that PG and TX synthesis is controlled by the regulation of PG- and TX-synthesizing enzymes. In this study, we examined the TX synthesis and the expression of TX-synthesizing enzymes in activated peripheral polymorphonuclear leukocytes (PMNs) obtained from children with bacterial infection. Blood samples were obtained from controls and patients with bacterial infection. A23187-stimulated production of TXB2, a stable metabolite of TXA2 in PMNs, was measured by a specific radioimmunoassay. The mRNA expression of cytosolic phospholipase A2 (cPLA2), cyclooxygenase (COX)-1, COX-2, and TXA2 synthase was determined by RT-PCR. The synthesis of TXB2 in PMNs was significantly increased in the patients [925.0 (550.0-1100.0) pg/106 cells], compared with the controls [550.0 (450.0-775.0) pg/106 cells]. The mRNA expression for cPLA2 and COX-2 in PMNs was also enhanced in the patients. The results indicate that TX production in PMNs is significantly increased through possible transcriptional mechanisms of cPLA2 and COX-2 during bacterial infection in children. The upregulation of TXA2 synthesis may contribute to the process of acute inflammatory reaction caused by bacterial infection. © 2003 Wiley-Liss, Inc.