Regulation of platelet-activating factor synthesis by acetyl-coenzyme A.
Human neutrophils (PMN) stimulated by tumor necrosis factor (TNF) synthesize and release platelet-activating factor (PAF) transiently. In the present investigation, we have examined the mechanism responsible for the down-regulation of PAF synthesis. The response of PMN is proportional to the occupancy of high-affinity TNF receptors on the PMN plasma membrane, as shown by binding assays with [125I]TNF. These receptors are down-regulated within 10 min of the addition of TNF; the receptors reappear after 60 min, but the PMN do not resume PAF synthesis. Further PAF synthesis is obtained by adding acetyl-coenzyme A (CoA) to the culture medium. However, this compound does not diffuse into PMN, as shown by incubating these cells with labeled acetyl-CoA. This finding suggests that PAF synthesis is regulated by the amount of acetyl-CoA available to the lyso-PAF: acetyltransferase on the cell plasma membrane. This acetyl-CoA is accessible to chemicals in the culture medium, since it is hydrolysed by hydroxylamine. The inhibition of PAF synthesis by hydroxylamine is reversed by adding acetyl-CoA. PAF synthesis in TNF-treated cells appears to be regulated either by the amount of acetyl-CoA available or by the ability to transfer acetyl-CoA from the cellular pool to the lyso-PAF: acetyltransferase.
Tetta
C
C
Laboratorio di Immunopatologia, Università di Torino, Italy.
Camussi
G
G
Bussolino
F
F
Baglioni
C
C
D000105:Acetyl Coenzyme A / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D010972:Platelet Activating Factor; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000105:Acetyl Coenzyme A