Alteration of lipid metabolism associated with the activation of mouse alveolar macrophages induced by 1 alpha, 25-dihydroxyvitamin D3.

We have reported that 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25-(OH)2D3] directly induces fusion and tumoricidal activity (activation) in murine alveolar macrophages. In this study we examined lipid metabolism associated with the fusion and activation of alveolar macrophages induced by 1 alpha, 25-(OH)2D3. Treatment of alveolar macrophages with 12 nM 1 alpha, 25-(OH)2D3 for 48 h caused a marked increase in incorporation of [14C]acetic acid and [14C]oleic acid into triacylglycerol. The macrophages treated with the vitamin began to fuse and show cytotoxicity at 48 h, whereas incorporation of the radioactive compounds into triacylglycerol started as early as 12 h after 1 alpha, 25-(OH)2D3 was added. The triacylglycerol synthesis induced by 1 alpha, 25-(OH)2D3 was greatly increased when 14C-labeled unsaturated fatty acids were used as tracers compared with 14C-labeled saturated fatty acids. The activity of diacylglycerol acyltransferase, which catalyzes the last step of the three acylations in triacylglycerol synthesis, was significantly higher in the macrophages treated with 1 alpha, 25-(OH)2D3 than in the control macrophages. Like 1 alpha, 25-(OH)2D3, retinoic acid and lypopolysaccharides also activated alveolar macrophages, but not induce any fusion. The activated macrophages cultured with retinoic acid or lypopolysaccharides also induced synthesis of triacylglycerol. These results indicate that 1 alpha, 25-(OH)2D3 induces the synthesis of triacylglycerol by preferentially incorporating unsaturated fatty acids into diacylglycerol, and that the alteration of lipid metabolism is related to the activation, rather than the fusion, of alveolar macrophages.