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Platelet-Activating Factor Inhibits the Secretion of Platelet-Activating Factor Acetylhydrolase by Human Decidual Macrophages

Department of Obstetrics and Gynecology (H.N., Y.K., K.N., J.Y., I.M.), Oita Medical University, Hasama, Oita 879-5593, Japan; and Departments of Biochemistry and Obstetrics-Gynecology (J.M.J.), University of Texas Southwestern Medical Center, Dallas, Texas 75390-9038

Address all correspondence and requests for reprints to: Hisashi Narahara, M.D., Department of Obstetrics and Gynecology, Oita Medical University, 1-1 Idaigaoka, Hasama, Oita 879-5593, Japan. E-mail: naraharh{at}oita-med.ac.jp.

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.

This work was supported, in part, by a Grant-in-Aid for Scientific Research (13671732) from the Ministry of Education, Science, and Culture of Japan.

Abbreviations: BAPTA/AM, Bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl)-ester; C-PAF, carbamyl-PAF; CSF, colony-stimulating factor; D-PBS, Dulbecco’s PBS; H-7, 1-(5-isoquinolinesulfonyl)-2-metylpiperazine; PAF, platelet-activating factor; PAF-AH, PAF-acetylhydrolase; PKC, protein kinase C; TPA, 12-O-tetradecanoylphobol 13-acetate.