Effects of endotoxins and cytokines on the secretion of platelet-activating factor-acetylhydrolase by human decidual macrophages.
OBJECTIVE
The aim was to clarify the role of platelet-activating factor in parturition, preterm labor, and premature rupture of membranes.


METHODS
Decidual macrophage populations were obtained by enzymic digestion, Ficoll-Paque centrifugation, or flow cytometric sorting. The effects of endotoxins and cytokines on platelet-activating factor-acetylhydrolase secretion by these cells were examined.


RESULTS
Lipopolysaccharide inhibited the platelet-activating factor-acetylhydrolase secretion by decidual macrophages. The inhibition was partially reversed by interleukin-1 receptor antagonist or by neutralizing antibodies against interleukin-1 alpha, interleukin-1 beta, or tumor necrosis factor-alpha. Tumor necrosis factor-alpha, interleukin-1 alpha, and interleukin-1 beta also decreased the enzyme secretion. The inhibitory actions of tumor necrosis factor-alpha and interleukin-1 beta were specifically neutralized by the corresponding antibodies. The effect of interleukin-1 alpha or interleukin-1 beta on the secretion was abolished by interleukin-1 receptor antagonist.


CONCLUSIONS
It is suggested that platelet-activating factor is involved in the pathogenesis of preterm labor or premature rupture of membranes caused by endotoxins and the subsequent activation of cytokine network.
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9051.
H
H
Narahara
J M
JM
Johnston
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000704:Analysis of Variance; D001667:Binding, Competitive; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D010741:Phospholipases A / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000502:physiology; D011247:Pregnancy; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D010972:Platelet Activating Factor; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase