Effect of octadecylmethylglycerophosphocholine and hexadecylmethylglycerol on arachidonic acylation or release in macrophages.

1-O-Octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-O-CH3) and 1-O-hexadecyl-2-O-methyl-sn-glycerol (hexadecylmethylglycerol) are dialkylglycerolipids poorly split by the lipolytic enzymes which can activate macrophages in culture. This study concerned the incorporation of [3H]arachidonate into glycerolipids of rat peritoneal macrophages and its subsequent release. Cells cultured with ET-18-O-CH3 or hexadecylmethylglycerol were labelled according to two procedures: (1) Cells were incubated first with dialkylglycerolipid and then with the tritiated arachidonate: hexadecylmethylglycerol was practically inactive. ET-18-O-CH3 inhibited acylation of arachidonate in cell glycerophospholipids (50%) and triglycerides (60%) during de novo glycerolipid synthesis, resulting in increased fatty acid radioactivity in cells. Both dialkylglycerolipids induced the release of tritiated eicosanoids and fatty acids in the medium. (2) Cells previously labelled with [3H]arachidonate were incubated with dialkylglycerolipid. Prelabelled glycerophospholipids and triglycerides were only slightly affected by ET-18-O-CH3 which was nonetheless more efficient than hexadecylmethylglycerol in decreasing cell triglyceride (50%) and glycerophospholipid (10%) synthesis. Both induced the release of eicosanoids and fatty acids into the medium. It is concluded that these agents, particularly ET-18-O-CH3, allowed moderate but significant amounts of eicosanoids and fatty acids to be maintained in the medium.