Differential synthesis of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine and platelet-activating factor by human inflammatory cells

Abstract

The synthesis of platelet-activating factor (PAF) and of the 1-acyl analogue of PAF, 1-acyl-2-acetyl-sn-glycero-3-phosphocholine (1-acyl-2-acetyl-GPC) was examined in seven human cell preparations (lung mast cell, basophil, endothelial cell, neutrophil, eosinophil, lung macrophage, platelet) and in human lung fragments. Cells were activated by either an appropriate receptor-mediated stimulus or by ionophore A23187 in the presence of [3H]acetate. All cell types, with the exception of the platelet, responded to stimulation with at least a twofold increase in the formation of labeled 1-radyl-2-acetyl-GPC as compared with control values. A23187 was the more potent stimulus in all cell types examined except the lung mast cell, in which anti-IgE consistently induced the synthesis of more 1-radyl-2-acetyl-GPC. Human lung fragments stimulated by anti-IgE, Ag Amb a I (after passive sensitization), or A23187 also incorporated [3H]acetate into 1-radyl-2-acetyl-GPC. Subclass analysis of 1-radyl-2-acetyl-GPC produced by each cell indicated that the cell types examined can be divided into two groups according to the predominant type of 1-radyl-2-acetyl-GPC produced. Some cell types (mast cell, basophil, endothelial cell) produced predominantly 1-acyl-2-acetyl-GPC, whereas others (neutrophil, eosinophil, lung macrophage) produced almost exclusively PAF. In some cell types, such as the lung mast cell and the basophil, A23187 stimulation increased the synthesis of PAF relative to 1-acyl-2-acetyl-GPC as compared with anti-IgE stimulation. In the lung fragments, [3H]acetate was predominantly incorporated into 1-acyl-2-acetyl-GPC upon IgE-mediated stimulation (anti-IgE, Amb a I) and into PAF upon A23187 stimulation. The differential production of these two phospholipids was confirmed by determining their sensitivity to lipase A1 and phospholipase A2 hydrolysis and by HPLC. These data demonstrate that 1-acyl-2-acetyl-GPC can be synthesized by a variety of human cells involved in the inflammatory reaction. This finding raises fundamental questions about the biologic role of this molecule and the factors regulating its synthesis within inflammatory cells.