Reichel H, Bishop J E, Koeffler H P, Norman A W
Department of Biochemistry, University of California, Riverside 92521.
Mol Cell Endocrinol. 1991 Feb;75(2):163-7. doi: 10.1016/0303-7207(91)90231-g.
Previous studies have demonstrated that human alveolar and bone marrow macrophages when activated in vitro can metabolize 25-hydroxyvitamin[3H]D3 to 1 alpha,25-dihydroxyvitamin[3H]D3; however, to date no animal models to study this system have been available. In the present study, cultured porcine pulmonary alveolar macrophages from two animals were assayed for their capability for metabolism of 25-hydroxyvitamin[3H]D3. The porcine alveolar macrophages constitutively produced a metabolite of 25-hydroxyvitamin[3H]D3 which was identified as 1 alpha,25-dihydroxyvitamin[3H]D3 by high performance liquid chromatography. The apparent KM was in the range of 300 nM. Unlike human macrophages, treatment of porcine alveolar macrophages with lipopolysaccharide did not stimulate 1 alpha,25-dihydroxyvitamin[3H]D3 production. Addition of 1 alpha,25-dihydroxyvitamin-D3 to macrophages cultures led to a sensitive proportional inhibition of 1 alpha,25-dihydroxyvitamin[3H]D3 synthesis.
以往的研究表明,人肺泡巨噬细胞和骨髓巨噬细胞在体外被激活时,能够将25-羟基维生素[3H]D3代谢为1α,25-二羟基维生素[3H]D3;然而,迄今为止尚未有用于研究该系统的动物模型。在本研究中,对来自两只动物的培养猪肺泡巨噬细胞进行了25-羟基维生素[3H]D3代谢能力的测定。猪肺泡巨噬细胞组成性地产生一种25-羟基维生素[3H]D3的代谢产物,通过高效液相色谱法鉴定为1α,25-二羟基维生素[3H]D3。表观米氏常数在300 nM范围内。与人类巨噬细胞不同,用脂多糖处理猪肺泡巨噬细胞不会刺激1α,25-二羟基维生素[3H]D3的产生。向巨噬细胞培养物中添加1α,25-二羟基维生素-D3会导致1α,25-二羟基维生素[3H]D3合成的敏感比例抑制。