Thromboxane synthesis is increased by upregulation of cytosolic phospholipase A2 and cyclooxygenase-2 in peripheral polymorphonuclear leukocytes during bacterial infection in childhood.
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.
Zaitsu
Masafumi
M
Department of Pediatrics, Faculty of Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. zaitsum@post.saga-med.ac.jp
Hamasaki
Yuhei
Y
Nishimura
Shinji
S
Matsuo
Muneaki
M
Fujita
Ichiro
I
Ishii
Eiichi
E
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
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