Biosynthesis of platelet-activating factor (PAF)acether). III. Formation of PAF-acether from synthetic substrates by stimulated murine macrophages.
Rat adherent macrophages (M phi) isolated from 2.5 x 10(6) peritoneal cells release 5.7 +/- 1.3 ng/ml platelet-activating factor (PAF-acether: 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) when stimulated by zymosan (Z). The yield of PAF-acether was increased to 13.8 +/- 1.8 ng/ml when stimulation occurred in the presence of 0.1 mM acetyl-CoA. That M phi used the acetyl moiety of acetyl-CoA to increase PAF-acether biosynthesis was demonstrated by the following criteria 1) as opposed to sodium acetate, malonyl-CoA, butyryl-CoA, palmitoyl-CoA, and CoA were inefficient in increasing the yield of PAF-acether; 2) radiolabeled PAF-acether was obtained after exposure of Z-stimulated M phi to 3H acetyl-CoA; actually, both radioactivity and biologic activity were eluted from HPLC with the same retention time as synthetic or natural PAF-acether; 3) after treatment with phospholipase A2, both radioactivity and biologic activity disappeared from these fractions. The yield of PAF-acether was further increased to 23.6 +/- 2.9 ng/ml by adding 0.5 microM totally synthetic 2-lyso PAF-acether (1-O-octadecyl-sn-glyceryl-3-phosphorylcholine) to Z-stimulated M phi cultured in the presence of acetyl-CoA. Again, using 3H 2-lyso PAF-acether, the formation of radiolabeled PAF-acether could be demonstrated. These results indicate that an acetyl-transferase is capable of synthesizing PAF-acether from 2-lyso PAF-acether and acetyl-CoA in intact M phi.
D000105:Acetyl Coenzyme A / Q000494:pharmacology; D000214:Acyl Coenzyme A / Q000494:pharmacology; D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D008244:Lysophosphatidylcholines / Q000096:biosynthesis* / Q000378:metabolism / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D008316:Malonyl Coenzyme A / Q000494:pharmacology; D051379:Mice; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000031:analogs & derivatives; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D015054:Zymosan / Q000494:pharmacology
D000214:Acyl Coenzyme A; D008244:Lysophosphatidylcholines; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D010171:Palmitoyl Coenzyme A; C024343:butyryl-coenzyme A; D008316:Malonyl Coenzyme A; D000105:Acetyl Coenzyme A; D015054:Zymosan