Adams J S, Gacad M A
J Exp Med. 1985 Apr 1;161(4):755-65. doi: 10.1084/jem.161.4.755.
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.
我们研究了来自结节病患者(无论有无临床异常钙稳态)的培养肺泡巨噬细胞(PAM)对维生素D3甾醇的1α-羟化作用。与天然存在的肾1α-羟化酶一样,PAM的1α-羟化反应对25-羟基维生素D3(25-OH-D3)具有高亲和力,并且更倾向于甾醇侧链中含有25-羟基的底物。与肾酶不同,即使在与75 nM 1,25-二羟基维生素D3 [1,25-(OH)2-D3]预孵育或暴露于高浓度底物(500 nM 25-OH-D3)后,PAM的1α-羟化机制也不伴有24-羟化活性。PAM的25-OH-D3-1α-羟化反应受到γ干扰素的刺激,并因暴露于糖皮质激素地塞米松而受到抑制。体外PAM羟化过程的特征似乎反映了肾外产生1,25-(OH)2-D3的效率以及糖皮质激素对结节病和钙代谢紊乱患者的治疗效果。