Biosynthesis of Paf-acether (platelet-activating factor). VII. Precursors of Paf-acether and acetyl-transferase...

Human polymorphonuclear neutrophils, monocytes, and lymphocytes were studied for their ability to synthesize Paf-acether when stimulated with the ionophore A 23187 (Io) or with specific secretagogues. When stimulated with Io, neutrophils produced 100 +/- 8.5 pmol Paf-acether 1 X 10(6) cells (mean +/- 1 SD, n = 5); monocytes were less efficient (44 +/- 3.3 pmol Paf-acether/1 X 10(6) cells), whereas lymphocytes were practically unable to form this mediator (1.0 +/- 0.4 pmol Paf-acether/1 X 10(6) cells). Neutrophils and monocytes released in the extracellular medium 49 and 37% of Paf-acether that they formed, respectively. We attempted to correlate the amount of Paf-acether produced by the various cell types with that of its precursors, 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine and 1-O-alkyl-sn-glycero-3-phosphocholine (2-lyso Paf-acether). In the three cell types, the amount of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine was sufficient to ensure the formation of 2-lyso Paf-acether and consequently that of Paf-acether. The quantity of 2-lyso Paf-acether formed appeared to be the limiting factor only in the case of the neutrophils. These cells increased their synthesis of Paf-acether in the presence of exogenous 2-lyso Paf-acether. To investigate the failure of lymphocytes to produce the mediator, the acetylating step of Paf-acether formation was studied, and we found a very weak activity (0.5 +/- 0.1 nmol Paf-acether/10 min/mg protein) in this cell type as opposed to monocytes (4.0 +/- 2.3 nmol Paf-acether/10 min/mg protein) and neutrophils (17.8 +/- 5.3 nmol Paf-acether/10 min/mg protein). These activities were doubled in Io-stimulated cells. Thus, the modulation of acetyl-transferase activity appears to be a key step in the regulation of Paf-acether biosynthesis. Also, the availability of 2-lyso Paf-acether could regulate Paf-acether synthesis in human neutrophils.