Document Detail

Secretion of platelet-activating factor acetylhydrolase following phorbol ester-stimulated differentiation of HL-60 cells.
MedLine Citation:
PMID:  8460940     Owner:  NLM     Status:  MEDLINE    
Platelet-activating factor (PAF) plays an important role in a number of biological processes ranging from inflammation to reproductive biology. We have reported that the enzyme that inactivates this potent autacoid, PAF-acetylhydrolase (PAF-AH), is decreased in maternal plasma during the latter stages of pregnancy. This enzyme is associated with the plasma lipoprotein fraction and therefore its tissue origin was thought to be the liver. Prescott and colleagues (J. Biol. Chem. 265, 17381, 1990) have reported that both a rat liver cell line (HepG2 cells) and human peripheral macrophages secrete PAF-AH of the plasma type. We have shown previously that the injection of rats with dexamethasone or medroxyprogesterone causes an increase and estrogen a decrease in the plasma PAF-AH activity. To clarify the mechanism of hormonal regulation of PAF-AH production, we employed a monocyte-macrophage model system to investigate the secretion of PAF-AH during differentiation. In the present study, we have demonstrated that a myelocytic leukemic cell line (HL-60) produces and secretes PAF-AH into a defined medium when the cells are differentiated into macrophages following stimulation by 12-O-tetradecanoylphorbol-13-acetate (TPA). The medium obtained from unstimulated HL-60 cells did not contain detectable amounts of PAF-AH activity. Stimulation with TPA caused a dose- and time-dependent increase in PAF-AH activity in the media. No increase in cell number was observed in the HL-60 cells during the culture period after the cells were treated with TPA. Cell lysis was excluded by the demonstration that the TPA-induced adherent cells excluded trypan blue and did not release lactate dehydrogenase activity into the medium. The increase in PAF-AH activity was inhibited by actinomycin D and cycloheximide. Dexamethasone and medroxyprogesterone markedly increased the secretion of PAF-AH by these cells, while estrogen was without effect. Bacterial endotoxin (lipopolysaccharide, LPS) inhibited the production of PAF-AH by these cells in a dose-dependent manner. The stimulation of PAF-AH secretion during differentiation of HL-60 cells and its modulation by LPS and steroid hormones may provide a useful model system for studying PAF metabolism during the inflammatory response and pregnancy.
H Narahara; R A Frenkel; J M Johnston
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  301     ISSN:  0003-9861     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  1993 Mar 
Date Detail:
Created Date:  1993-04-23     Completed Date:  1993-04-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  275-81     Citation Subset:  IM    
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9051.
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MeSH Terms
1-Alkyl-2-acetylglycerophosphocholine Esterase
Cell Differentiation / drug effects*
Dexamethasone / pharmacology
Dose-Response Relationship, Drug
Ethinyl Estradiol / pharmacology
Insulin / pharmacology
Lipopolysaccharides / pharmacology
Macrophages / drug effects,  enzymology*
Medroxyprogesterone / pharmacology
Monocytes / drug effects,  enzymology*
Phospholipases A / secretion*
Tetradecanoylphorbol Acetate / pharmacology*
Time Factors
Transferrin / pharmacology
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Lipopolysaccharides; 11061-68-0/Insulin; 11096-37-0/Transferrin; 16561-29-8/Tetradecanoylphorbol Acetate; 50-02-2/Dexamethasone; 520-85-4/Medroxyprogesterone; 57-63-6/Ethinyl Estradiol; EC 3.1.1.-/Phospholipases A; EC Esterase

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