Biosynthesis of platelet-activating factor and its 1O-acyl analogue by liver fat-storing cells.
OBJECTIVE
Platelet-activating factor (PAF) is an important mediator of proinflammatory cell-to-cell interactions with powerful vasoactive properties. We evaluated the biosynthesis of PAF by cultured human fat-storing cells (FSC), liver-specific pericytes involved in the inflammatory and fibrogenic process of liver tissue.


METHODS
PAF synthesis was evaluated by measuring [3H]acetate incorporation under basal conditions and upon stimulation with A23187, thrombin, and lipopolysaccharide. Further analysis of PAF species synthesized by FSC was performed using gas chromatography/mass spectrometry.


RESULTS
All stimuli induced a significant increase of basal PAF synthesis by FSC. Further analysis showed that > 50% of the newly synthesized PAF species was secreted whereas the remaining fraction was cell-associated. PAF species produced by FSC were able to induce aggregation of rabbit washed platelets with an effectiveness correspondent to 10(-9) mol/L authentic PAF. Gas chromatography/mass spectrometry analysis revealed that a large percentage (74%) of PAF-like lipids synthesized by FSC consisted of 1O-acyl PAF. Finally, stimulation of FSC with PAF caused an increase in cytosolic free calcium, thus suggesting a possible involvement of this pericyte in the well-known effects of PAF on portal pressure.


CONCLUSIONS
These results expand the available knowledge concerning the role of PAF in conditions characterized by extensive activation and damage of the liver sinusoidal endothelium and decreased hepatic scavenger activity.
Pinzani
M
M
Istituto di Clinica Medica II, Università di Firenze, Italy.
Carloni
V
V
Marra
F
F
Riccardi
D
D
Laffi
G
G
Gentilini
P
P
D000085:Acetates / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D013917:Thrombin / Q000494:pharmacology; D014316:Tritium
D000085:Acetates; D008055:Lipids; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D014316:Tritium; D000001:Calcimycin; D013917:Thrombin