Platelet-activating factor (PAF) stimulates the production of PAF acetylhydrolase by the human hepatoma cell line, HepG2.

Abstract

The human hepatoma cell line, HepG2, secreted an activity that degrades platelet-activating factor (PAF) by the hydrolysis ofthe sn-2 acetyl group. This activity was Ca"+ independent, inhibited by diisopropylfluorophosphate but not by p-bromophenacyl bromide, and resistant to treatment with trypsin or pronase. Separation of HepG2-conditioned medium by gel filtration disclosed that the activity was associated with lipoproteins. An antiserum against PAF acetylhydrolase immunoprecipitated this activity. It was not recognized by an antibody against lecithin:cholesterol acyltransferase (LCAT), which also is secreted by HepG2 cells. Therefore the phospholipase A2 activity of LCAT was excluded as a source of the observed activity. PAF added to the culture medium stimulated the secretion of the PAF-degrading activity by HepG2 cells, while lyso-PAF was inactive. Maximal stimulation was observed with 5 ng/ml PAF, which induced a fivefold increase. The presence of 5 ng/ml PAF enhanced the secretion of [35Sjmethionine-labeled PAF acetylhydrolase and cycloheximide inhibited both the basal and PAF-stimulated secretion of the labeled enzyme.We conclude that HepG2 cells produce PAF acetylhydrolase. The liver may be a major source of plasma PAF acetylhydrolase, and PAF may induce the production of its inactivating enzyme by the liver. (J. Clin.

The Expression and Localization of Plasma Platelet-activating Factor Acetylhydrolase in Endotoxemic Rats

“…In addition, PAF stimulated the secretion of PAF acetylhydrolase in the human hepatoma cell line, Hep G2, in a cycloheximide-sensitive fashion (24). Liver PAF levels are elevated significantly 3 h after LPS exposure in this endotoxin exposure model.…”

Modulation of oxidative stress, inflammation, and atherosclerosis by lipoprotein-associated phospholipase A2

“…Independent studies have shown that PAF, which bears structural resemblance to fragmented, short-chain phospholipids, upregulates expression of Lp-PLA 2 mRNA in monocyte/macrophages ( 48 ) and HepG2 cells ( 53 ). Consistently, a recent study reported elevated plasma levels of both PAF and Lp-PLA 2 mass in a cohort of coronary heart disease (CHD) patients compared with a control group ( 54 ).…”

Inhibition of Platelet-Activating Factor (PAF) Acetylhydrolase by Methyl Arachidonyl Fluorophosphonate Potentiates PAF Synthesis in Thrombin-Stimulated Human Coronary Artery Endothelial Cells

“…Several studies have determined that the level of PAF accumulation is determined by the PAF-AH activity (Touqui et al, 1985;Suzuki et al, 1988;Elstad et al, 1989). In addition, the magnitude of the inflammatory response to PAF may function in an autoregulatory manner because increased production of PAF stimulates the expression of PAF-AH (Satoh et al, 1991). Thus, it follows that inhibition of PAF-AH would propagate the PAF-mediated inflammatory response.…”