结节病患者培养的肺泡巨噬细胞对维生素D3甾醇1α-羟化作用的特性研究
Characterization of 1 alpha-hydroxylation of vitamin D3 sterols by cultured alveolar macrophages from patients with sarcoidosis.
作者信息
Adams J S, Gacad M A
出版信息
J Exp Med. 1985 Apr 1;161(4):755-65. doi: 10.1084/jem.161.4.755.
Abstract
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.
摘要
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。
相似文献
1
Characterization of 1 alpha-hydroxylation of vitamin D3 sterols by cultured alveolar macrophages from patients with sarcoidosis.结节病患者培养的肺泡巨噬细胞对维生素D3甾醇1α-羟化作用的特性研究
J Exp Med. 1985 Apr 1;161(4):755-65. doi: 10.1084/jem.161.4.755.
2
Regulation of 1,25-dihydroxyvitamin D3 production by cultured alveolar macrophages from normal human donors and from patients with pulmonary sarcoidosis.来自正常人类供体和肺结节病患者的培养肺泡巨噬细胞对1,25 - 二羟基维生素D3产生的调节作用。
J Clin Endocrinol Metab. 1987 Dec;65(6):1201-9. doi: 10.1210/jcem-65-6-1201.
3
Metabolism of 25-hydroxyvitamin D3 by cultured pulmonary alveolar macrophages in sarcoidosis.结节病中培养的肺泡巨噬细胞对25-羟基维生素D3的代谢
J Clin Invest. 1983 Nov;72(5):1856-60. doi: 10.1172/JCI111147.
4
A role for endogenous arachidonate metabolites in the regulated expression of the 25-hydroxyvitamin D-1-hydroxylation reaction in cultured alveolar macrophages from patients with sarcoidosis.内源性花生四烯酸代谢产物在结节病患者培养的肺泡巨噬细胞中25-羟基维生素D-1-羟化反应的调控表达中的作用。
J Clin Endocrinol Metab. 1990 Mar;70(3):595-600. doi: 10.1210/jcem-70-3-595.
5
Isolation and structural identification of 1,25-dihydroxyvitamin D3 produced by cultured alveolar macrophages in sarcoidosis.结节病中培养的肺泡巨噬细胞产生的1,25 - 二羟维生素D3的分离与结构鉴定
J Clin Endocrinol Metab. 1985 May;60(5):960-6. doi: 10.1210/jcem-60-5-960.
6
Biochemical indicators of disordered vitamin D and calcium homeostasis in sarcoidosis.结节病中维生素D和钙稳态紊乱的生化指标
Sarcoidosis. 1986 Mar;3(1):1-6.
7
Ketoconazole decreases the serum 1,25-dihydroxyvitamin D and calcium concentration in sarcoidosis-associated hypercalcemia.酮康唑可降低结节病相关性高钙血症患者的血清1,25 - 二羟维生素D和钙浓度。
J Clin Endocrinol Metab. 1990 Apr;70(4):1090-5. doi: 10.1210/jcem-70-4-1090.
8
Production of 1,25-dihydroxyvitamin D3 by pulmonary alveolar macrophages from patients with sarcoidosis.结节病患者肺泡巨噬细胞产生1,25 - 二羟维生素D3 。
Ann N Y Acad Sci. 1986;465:587-94. doi: 10.1111/j.1749-6632.1986.tb18535.x.
9
Potentiation of the macrophage 25-hydroxyvitamin D-1-hydroxylation reaction by human tuberculous pleural effusion fluid.人结核性胸腔积液对巨噬细胞25-羟基维生素D-1-羟化反应的增强作用。
J Clin Endocrinol Metab. 1989 Aug;69(2):457-60. doi: 10.1210/jcem-69-2-457.
引用本文的文献
1
Targeting Neuronal Alpha7 Nicotinic Acetylcholine Receptor Upregulation in Age-Related Neurological Disorders.靶向年龄相关性神经疾病中神经元α7烟碱型乙酰胆碱受体上调
Cell Mol Neurobiol. 2025 Jul 16;45(1):70. doi: 10.1007/s10571-025-01586-6.
2
Hypercalcemia of Malignancy: Mechanisms and Therapeutic Implications of Concurrently Elevated PTHrP and Calcitriol.恶性肿瘤高钙血症：甲状旁腺激素相关蛋白（PTHrP）和骨化三醇同时升高的机制及治疗意义
J Endocr Soc. 2025 Jul 14;9(9):bvaf104. doi: 10.1210/jendso/bvaf104. eCollection 2025 Sep.
3
An Atypical Case of Extrapulmonary Sarcoidosis with Severe Hypercalcemia as Initial Presentation, Successfully Treated with Glucocorticoids.以严重高钙血症为首发表现的肺外结节病非典型病例，经糖皮质激素成功治疗。
Clin Pract. 2024 Jun 29;14(4):1264-1269. doi: 10.3390/clinpract14040102.
4
Pneumocystis jirovecii pneumonia presenting with severe, refractory hypercalcaemia in an immunosuppressed renal transplant patient: Review of the literature and novel biochemical insights.免疫抑制肾移植患者发生以严重、难治性高钙血症为表现的卡氏肺孢子菌肺炎：文献复习和新的生化见解。
Clin Med (Lond). 2024 Jan;24(1):100011. doi: 10.1016/j.clinme.2023.100011. Epub 2024 Jan 8.
5
Vitamin D and Its Analogues: From Differences in Molecular Mechanisms to Potential Benefits of Adapted Use in the Treatment of Alzheimer's Disease.维生素 D 及其类似物：从分子机制的差异到在阿尔茨海默病治疗中适应性使用的潜在益处。
Nutrients. 2023 Mar 30;15(7):1684. doi: 10.3390/nu15071684.
6
Subcutaneous fat necrosis in newborns: a systematic literature review of case reports and model of pathophysiology.新生儿皮下脂肪坏死：病例报告及病理生理模型的系统文献综述
Mol Cell Pediatr. 2022 Nov 24;9(1):18. doi: 10.1186/s40348-022-00151-1.
7
Vitamin D in Systemic Sclerosis: A Review.维生素 D 在系统性硬化症中的作用：综述。
Nutrients. 2022 Sep 21;14(19):3908. doi: 10.3390/nu14193908.
8
Calcitriol-Mediated Hypercalcemia, Somatostatin Receptors Expression and 25-Hydroxyvitamin D-1α- Hydroxylase in GIST Tumors.钙三醇介导的高钙血症、生长抑素受体表达与 GIST 肿瘤中 25-羟维生素 D-1α-羟化酶。
Front Endocrinol (Lausanne). 2022 Jan 26;12:812385. doi: 10.3389/fendo.2021.812385. eCollection 2021.
9
Vitamin D, infections and immunity.维生素 D、感染与免疫。
Rev Endocr Metab Disord. 2022 Apr;23(2):265-277. doi: 10.1007/s11154-021-09679-5. Epub 2021 Jul 29.
10
Implications of Vitamin D Research in Chickens can Advance Human Nutrition and Perspectives for the Future.鸡维生素D研究的启示可推动人类营养及未来展望。
Curr Dev Nutr. 2021 Feb 25;5(5):nzab018. doi: 10.1093/cdn/nzab018. eCollection 2021 May.
本文引用的文献
1
Effect of cortisone on calcium metabolism in sarcoidosis with hypercalcaemia; possibly antagonistic actions of cortisone and vitamin D.可的松对结节病伴高钙血症患者钙代谢的影响；可的松与维生素D可能存在的拮抗作用。
Lancet. 1954 Oct 9;267(6841):720-4. doi: 10.1016/s0140-6736(54)90492-4.
2
Lymphokines enhance the capacity of human monocytes to secret reactive oxygen intermediates.淋巴因子可增强人类单核细胞分泌活性氧中间产物的能力。
J Clin Invest. 1982 Nov;70(5):1042-8. doi: 10.1172/jci110691.
3
Regulation of 25 hydroxyvitamin D3 1-hydroxylase in serum-free monolayer culture of mouse kidney.小鼠肾脏无血清单层培养中25-羟基维生素D3 1-羟化酶的调控
Endocrinology. 1982 Mar;110(3):1073-5. doi: 10.1210/endo-110-3-1073.
4
The human alveolar macrophage.人类肺泡巨噬细胞。
Methods Cell Biol. 1980;21A:95-105. doi: 10.1016/s0091-679x(08)60760-8.
5
Regulation of the metabolism of vitamin D.维生素D代谢的调节
Physiol Rev. 1980 Apr;60(2):551-613. doi: 10.1152/physrev.1980.60.2.551.
6
The synthesis of dihydroxylated vitamin D metabolites by human renal mitochondria.人肾线粒体中二羟基化维生素D代谢产物的合成
J Clin Endocrinol Metab. 1981 Aug;53(2):450-2. doi: 10.1210/jcem-53-2-450.
7
In vitro metabolism of 25-hydroxyvitamin D3 by isolated rat kidney cells.25-羟基维生素D3在分离的大鼠肾细胞中的体外代谢
Proc Natl Acad Sci U S A. 1980 Mar;77(3):1537-40. doi: 10.1073/pnas.77.3.1537.
8
Catalytic activity of partially purified renal 25-hydroxyvitamin D hydroxylases from vitamin D-deficient and vitamin D-replete rats.来自维生素D缺乏和维生素D充足大鼠的部分纯化的肾25-羟维生素D羟化酶的催化活性。
J Biol Chem. 1982 Nov 10;257(21):12995-3000.
9
Abnormal regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase activity by calcium and calcitonin in renal cortex from hypophosphatemic (Hyp) mice.低磷血症（Hyp）小鼠肾皮质中钙和降钙素对25-羟基维生素D3-1α-羟化酶活性的异常调节。
Endocrinology. 1984 Apr;114(4):1203-7. doi: 10.1210/endo-114-4-1203.
10
Metabolism of 25-hydroxyvitamin D3 by cultured pulmonary alveolar macrophages in sarcoidosis.结节病中培养的肺泡巨噬细胞对25-羟基维生素D3的代谢
J Clin Invest. 1983 Nov;72(5):1856-60. doi: 10.1172/JCI111147.
Zotero 插件