Platelet-activating factor inhibits the secretion of platelet-activating factor acetylhydrolase by human decidual macrophages.
To clarify the role of platelet-activating factor (PAF) in parturition, the effects of PAF on the secretion of PAF-acetylhydrolase (PAF-AH), a PAF-inactivating enzyme, by decidual macrophage populations were examined. The cells were isolated from human decidual tissue by enzymatic digestion, Ficoll-Paque centrifugation, or flow cytometric sorting. The nonhydrolyzable agonist of PAF, carbamyl-PAF (C-PAF), inhibited the secretion of PAF-AH by either decidual cells or flow cytometrically purified decidual macrophages. A specific PAF receptor antagonist, WEB 2086, blocked the C-PAF-induced inhibition. Lyso-PAF, a metabolite of PAF, had no effect on the enzyme secretion. An intracellular calcium channel blocker, bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl)-ester, partially blocked the inhibition by C-PAF, whereas extracellular calcium channel blockers, nifedipine and verapamil, were without effect. The inhibitory effect of C-PAF was also partially blocked by protein kinase C (PKC) inhibitors, sphingosine and H-7. A PKC activator, 12-O-tetradecanoylphobol 13-acetate, decreased the secretion of PAF-AH. The decrease was abolished by the addition of sphingosine and H-7. It is suggested that PAF inhibits the PAF-AH secretion by decidual macrophages and that the inhibitory action is mediated by a signal transduction mechanism involving intracellular calcium and PKC.
Narahara
Hisashi
H
Department of Obstetrics and Gynecology, Oita Medical University, Hasama, Oita 879-5593, Japan. naraharh@oita-med.ac.jp
Kawano
Yasushi
Y
Nasu
Kaei
K
Yoshimatsu
Jun
J
Johnston
John M
JM
Miyakawa
Isao
I
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000819:agonists / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism
D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; C053479:1-O-hexadecyl-2-N-methylcarbamylphosphatidylcholine; D011493:Protein Kinase C; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D002118:Calcium