Interleukin 1 stimulates platelet-activating factor production in cultured human endothelial cells.
Monocyte-derived interleukin 1 (IL-1) was found to be a potent inducer of platelet-activating factor (PAF) in cultured human vascular endothelial cells (HEC). The product was identified as PAF by its behavior in chromatographic systems, its recovery of biological activity, and its physico-chemical properties and susceptibility to lipases. The response of HEC to IL-1 was concentration-dependent, took more than 2 h to become apparent, and decreased after 18 h of incubation. Most of the PAF produced was cell-associated and only a small amount (about 25% of the total) was released in the culture medium. To study the mechanism of IL-1-induced HEC-PAF production we tested the activity of 1-O-alkyl-sn-glycero-3-phosphocholine:acetyl/coenzyme A acetyltransferase in HEC. Acetyltransferase activity measured in IL-1-stimulated HEC lysates showed a three to five times greater maximum velocity, but the same Michaelis constant, as untreated cells. The regulation of PAF generation in HEC by IL-1 may be an important aspect of the two-way interaction between immunocompetent cells and vascular tissue.
Bussolino
F
F
Breviario
F
F
Tetta
C
C
Aglietta
M
M
Mantovani
A
A
Dejana
E
E
D000105:Acetyl Coenzyme A / Q000494:pharmacology; D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000096:biosynthesis*
D006629:Hirudins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D000105:Acetyl Coenzyme A; D003513:Cycloheximide; D000101:Acetyl-CoA C-Acetyltransferase; D001241:Aspirin