title: 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 TXB(2), a stable metabolite of TXA(2) in PMNs, was measured by a specific radioimmunoassay. The mRNA expression of cytosolic phospholipase A(2) (cPLA(2)), cyclooxygenase (COX)-1, COX-2, and TXA(2) synthase was determined by RT-PCR. The synthesis of TXB(2) in PMNs was significantly increased in the patients [925.0 (550.0-1100.0) pg/10(6) cells], compared with the controls [550.0 (450.0-775.0) pg/10(6) cells]. The mRNA expression for cPLA(2) 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 cPLA(2) and COX-2 during bacterial infection in children. The upregulation of TXA(2) synthesis may contribute to the process of acute inflammatory reaction caused by bacterial infection.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. zaitsum@post.saga-med.ac.jp
authors.forename: Masafumi
authors.initials: M
authors.lastname: Zaitsu
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Hamasaki
authors.forename: Shinji
authors.initials: S
authors.lastname: Nishimura
authors.forename: Muneaki
authors.initials: M
authors.lastname: Matsuo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Fujita
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D003600:Cytosol / Q000201:enzymology; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010741:Phospholipases A / Q000235:genetics*; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D013928:Thromboxane A2 / Q000235:genetics; D013929:Thromboxane B2 / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D000900:Anti-Bacterial Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D000001:Calcimycin; D013929:Thromboxane B2; D013928:Thromboxane A2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2