Biosynthesis of paf-acether. XVII. Regulation by the CoA-independent transacylase in human neutrophils.
Treatment of intact human polymorphonuclear neutrophils (PMN) with low concentrations of phorbol myristate acetate (PMA, 1-10 ng/ml) induced paf-acether (paf) and lyso paf formation, arachidonate release, and simultaneous inhibition of CoA-independent lyso paf: transacylase as assayed in a cell-free system. Inhibition of [3H]lyso paf reacylation was also observed when it was exogenously added to the PMA-treated intact PMN. When higher concentrations of PMA (40-100 ng/ml) were used, paf biosynthesis was severely impaired and the level of the CoA-independent transacylase activity returned to basal level. Since lyso paf appears to be the substrate for PMA-activated paf formation (remodeling pathway), we showed that [14C]acetate was incorporated into the paf molecule. By contrast, labeling with [3H]choline was not appropriate in this model. The presented results are against the involvement of a de novo route in paf synthesis initiated by PMA and open a new possibility of an important role for the CoA-independent transacylase in controlling the level of lyso paf availability for paf formation.
Ninio
E
E
INSERM U200, Clamart, France.
Breton
M
M
Bidault
J
J
Colard
O
O
D000085:Acetates / Q000097:blood; D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000097:blood; D000217:Acyltransferases / Q000097:blood*; D002794:Choline / Q000097:blood; D006706:Homeostasis; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000085:Acetates; D010972:Platelet Activating Factor; D000217:Acyltransferases; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase; D002794:Choline; D013755:Tetradecanoylphorbol Acetate