Characterization of 1 alpha-hydroxylation of vitamin D3 sterols by cultured alveolar macrophages from patients with sarcoidosis.
Characterization of 1 alpha-hydroxylation of vitamin D3 sterols by cultured alveolar macrophages from patients with sarcoidosis.
复制标题
DOI：
10.1084/jem.161.4.755
复制
发表时间：
1985-04-01
期刊：
影响因子：
--
通讯作者：
Gacad MA
中科院分区：
文献类型：
--
作者：
Adams JS;Gacad MA
我们研究了有或没有临床钙稳态异常的结节病患者培养的肺泡巨噬细胞(PAM)对维生素D3甾醇的1α羟化作用。与自然产生的肾脏1α-羟基酶一样，PAM 1α-羟基化反应对25-羟基维生素D3(25-OH-D3)表现出高亲和力，并偏好在甾醇侧链中含有25-羟基的底物。与肾酶不同，PAM 1α-羟化机制不伴随24-羟化活性，即使在与75 NM 1，25-二羟基维生素D3[1，25-(OH)2-D3]预先孵育或暴露于高浓度底物(500 NM 25-OH-D3)后也是如此。PAM 25-OH-D3-1α-羟化反应受干扰素刺激，糖皮质激素地塞米松抑制。PAM体外羟化过程的特征似乎反映了肾外产生1，25-(OH)2-D3的效率和糖皮质激素对结节病和钙代谢紊乱患者的治疗效果。
We investigated the 1 alpha-hydroxylation of vitamin D3 sterols by cultured pulmonary alveolar macrophages (PAM) from patients with sarcoidosis with or without clinically abnormal calcium homeostasis. Like the naturally occurring renal 1 alpha-hydroxylase, the PAM 1 alpha- hydroxylation reaction exhibited a high affinity for 25-hydroxyvitamin D3 (25-OH-D3) and a preference for substrates containing a 25-hydroxyl group in the side chain of the sterol. Unlike the renal enzyme, the PAM 1 alpha-hydroxylating mechanism was not accompanied by 24-hydroxylating activity, even after preincubation with 75 nM 1,25-dihydroxyvitamin D3 [1,25-(OH)2-D3] or exposure to high concentrations of substrate (500 nM 25-OH-D3). The PAM 25-OH-D3-1 alpha-hydroxylation reaction was stimulated by gamma interferon and inhibited by exposure to the glucocorticoid dexamethasone. The characteristics of the PAM hydroxylation process in vitro appear to reflect the efficiency of the extrarenal production of 1,25-(OH)2-D3 and the therapeutic efficacy of glucocorticoids in patients with sarcoidosis and disordered calcium metabolism.