Liver cells secrete the plasma form of platelet-activating factor acetylhydrolase.
Platelet-activating factor (PAF) is a phospholipid (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) with diverse physiological effects. It has been implicated as a mediator of inflammation, allergy, shock, and thrombosis. Plasma contains an enzyme, PAF acetylhydrolase, that catalyzes the degradation of PAF, and the level of this enzyme may regulate the concentration of PAF in the blood and extracellular spaces under some conditions. Thus, the cellular source(s) of this enzyme and the factors that regulate its synthesis and secretion are issues that may have important physiological and pathological implications. We found that cultures of Hep G2, a human hepatocarcinoma line, secreted PAF acetylhydrolase activity. Optimal secretion occurred in medium that contained serum, and the newly secreted PAF acetylhydrolase was associated with high density and low density lipoproteins (LDL and HDL, respectively), just as the enzyme is in plasma. In the absence of serum. PAF acetylhydrolase was secreted with a particle that had a density similar to HDL. Apolipoproteins B and E were found in the same fractions. We tested the effects of a variety of hormones on the secretion of PAF acetylhydrolase and found that secretion was inhibited by 17 alpha-ethynylestradiol with a maximal effect at 30 microM. This may account for the observation of others that estrogens reduce the activity of PAF acetylhydrolase in the plasma. The PAF acetylhydrolase secreted by Hep G2 cells appeared to be identical to the enzyme in human plasma based on substrate specificity, association with LDL and HDL, response to inhibitors, and reactivity with antibodies against the plasma PAF acetylhydrolase. In conclusion, we have demonstrated that hepatocytes in culture secrete a PAF acetylhydrolase that is apparently identical to the plasma form. The secretion is constitutive but may also be regulated in response to hormonal stimulation.
Tarbet
E B
EB
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City 84112.
Stafforini
D M
DM
Elstad
M R
MR
Zimmerman
G A
GA
McIntyre
T M
TM
Prescott
S M
SM
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D006528:Carcinoma, Hepatocellular; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D010741:Phospholipases A / Q000097:blood / Q000378:metabolism*; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D004967:Estrogens; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase