A product of activated human granulocytes stimulates prostaglandin E2 synthesis in human amnion cells.
Cell-free supernatant from formylmethionyl-leucyl-phenylalanine (fMLP)-activated granulocytes causes a time- and concentration-dependent stimulation of prostaglandin E2 (PGE2) production in amnion cells. PGE2 concentration in the culture medium after 36 h treatment with granulocyte supernatant (from 40 x 10(6) granulocytes/ml of amnion cell medium), 1.49 +/- 0.71 pg/ng DNA (n = 13), was significantly higher (p = 0.0015) than in control cells (0.33 +/- 0.23 pg/ng DNA, n = 13). Indomethacin abolished this stimulation. Granulocyte supernatant and human epidermal growth factor (hEGF) had an additive effect on amnion cell PGE2 production. Catalase, superoxide dismutase (SOD), protease inhibitors or the platelet-activating factor (PAF) antagonist L-659,989 had no effect. Actinomycin D, cycloheximide and mepacrine reduced the PGE2 production. The phospholipase A2 activity present in granulocyte supernatants was resistant to heating, whereas heating decreased their PGE2-stimulating activity by 92%. Exogenous phospholipase A2 had no effect on PGE2 synthesis. The granulocyte product could be precipitated with ammonium sulphate. On gel filtration of supernatant, two peaks of PGE2-synthesis stimulating activity were obtained (molecular weights 12,000 and 60,000). This data serve to explain the association of chorioamnionitis with preterm labor: activated granulocytes release a protein(s) that induces prostaglandin production in amnion cells, and thus promote labor.
Bry
K
K
Department of Pediatrics, University of Helsinki, Finland.
Hallman
M
M
D000650:Amnion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002821:Chorioamnionitis / Q000150:complications / Q000503:physiopathology; D003571:Cytochalasin B / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers; D006098:Granulocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007743:Labor, Obstetric / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D007752:Obstetric Labor, Premature / Q000209:etiology / Q000503:physiopathology; D010741:Phospholipases A / Q000032:analysis*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D011247:Pregnancy; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013268:Stimulation, Chemical
D016166:Free Radical Scavengers; D010972:Platelet Activating Factor; D011500:Protein Synthesis Inhibitors; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D004815:Epidermal Growth Factor; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone; D007213:Indomethacin