Biosynthesis of platelet-activating factor (PAF) induced by chemotactic peptide is modulated at the lyso-PAF:acetyl-CoA acetyltransferase level by calcium transient and phosphatidic acid.
The chemotactic peptide fMLP (N-formyl-methionyl-leucyl-phenylalanine) induced the production of platelet-activating factor (PAF) by human polymorphonuclear leukocytes (PMN) incubated with cytochalasin B (CB). CoA-independent transacylase showed similar activity in both resting and stimulated PMN, and PAF production only occurred when lyso-PAF:acetyl-CoA acetyltransferase had been converted into the high activity form. PAF formation was coincidental with an increase of the concentration of cytosolic Ca2+ ([Ca2+]i), and with an enhanced formation of 1-O-[3H]alkyl-2-acyl-sn-glycerol. Both fMLP-induced PAF production and the activation of lyso-PAF:acetyl-CoA acetyltransferase were diminished by propranolol. Since several molecular species of phosphatidic acid (PA) produced an inhibition of both PAF production and acetyltransferase activation on intact cells, a portion of the inhibitory effect of propranolol was related to the accumulation of PA. Furthermore, whereas CB increased both the extent and the duration of the fMLP-induced [Ca2+]i transient, propranolol was found to inhibit the CB-induced increase of the [Ca2+]i transient. These data indicate that both the attenuation of [Ca2+]i transient and the accumulation of PA may operate as termination signals for PAF production by actin on lyso-PAF:acetyl-CoA acetyltransferase.
Garcia
C
C
Fundación Jiménez Díaz, Madrid, Spain.
Montero
M
M
Alvarez
J
J
Sanchez Crespo
M
M
D000123:Acetyltransferases / Q000378:metabolism*; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D004075:Diglycerides / Q000494:pharmacology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D011433:Propranolol / Q000494:pharmacology
D004075:Diglycerides; D010712:Phosphatidic Acids; D010972:Platelet Activating Factor; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011433:Propranolol; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase; D010741:Phospholipases A; D002118:Calcium