肺泡巨噬细胞中25-羟基维生素D3 1α-羟化酶基因表达与结节病活动度的相关性

Correlation between 25-hydroxyvitamin D3 1 alpha-hydroxylase gene expression in alveolar macrophages and the activity of sarcoidosis.

作者信息

Inui N, Murayama A, Sasaki S, Suda T, Chida K, Kato S, Nakamura H

机构信息

Department of Internal Medicine, Second Division, Hamamatsu University School of Medicine, Hamamatsu, Japan.

出版信息

Am J Med. 2001 Jun 15;110(9):687-93. doi: 10.1016/s0002-9343(01)00724-0.

DOI:10.1016/s0002-9343(01)00724-0

PMID:11403752

Abstract

PURPOSE

To demonstrate expression of the 25-hydroxyvitamin D3 1 alpha-hydroxylase (1 alpha-hydroxylase) gene in human alveolar macrophages and measure the correlations among the 1 alpha-hydroxylase mRNA level, the activity of sarcoidosis, and calcium metabolism.

SUBJECTS AND METHODS

We examined 7 patients with sarcoidosis and 6 control patients with other pulmonary disorders who underwent bronchoalveolar lavage. Levels of 1 alpha-hydroxylase mRNA were measured by semiquantitative polymerase chain reaction amplification. We measured serum levels of calcium, ionized calcium, parathyroid hormone, calcitriol (1,25-dihydroxyvitamin D3), and 25-hydroxyvitamin D3 to evaluate calcium metabolism. To estimate the activity of sarcoidosis, we measured the cell count, the CD4/CD8 ratio in bronchoalveolar lavage cells, and the serum angiotensin-converting enzyme (ACE) activity.

RESULTS

Expression of 1 alpha-hydroxylase was demonstrated in purified human alveolar macrophages. The 1 alpha-hydroxylase mRNA levels in bronchoalveolar lavage cells were fivefold higher in sarcoidosis patients than in control patients (10.8 +/- 3.6 vs. 2.2 +/- 1.4, P <0.003). Among all patients studied, there were significant correlations between the 1 alpha-hydroxylase mRNA level in bronchoalveolar lavage samples and the percentage of alveolar lymphocytes (r = 0.83, P <0.005), the CD4/CD8 ratio (r = 0.77, P <0.02), serum ACE level (r = 0.58, P <0.05), serum ionized calcium level (r = 0.58, P <0.05), and the calcitriol/25-hydroxyvitamin D3 ratio (r = 0.57, P <0.05). In the sarcoidosis patients, a significant correlation was also observed between 1 alpha-hydroxylase mRNA and the percentage of alveolar lymphocytes (r = 0.82, P <0.05).

CONCLUSION

There is a correlation between 1 alpha-hydroxylase gene expression in alveolar macrophages with the activity of sarcoidosis and its associated disturbances in calcium metabolism.

摘要

目的

证实人肺泡巨噬细胞中25-羟维生素D3 1α-羟化酶（1α-羟化酶）基因的表达，并测定1α-羟化酶mRNA水平、结节病活动度和钙代谢之间的相关性。

对象与方法

我们检查了7例结节病患者和6例患有其他肺部疾病并接受支气管肺泡灌洗的对照患者。通过半定量聚合酶链反应扩增测定1α-羟化酶mRNA水平。我们测定血清钙、离子钙、甲状旁腺激素、骨化三醇（1,25-二羟维生素D3）和25-羟维生素D3水平以评估钙代谢。为评估结节病的活动度，我们测定了支气管肺泡灌洗细胞的细胞计数、CD4/CD8比值以及血清血管紧张素转换酶（ACE）活性。

结果

在纯化的人肺泡巨噬细胞中证实了1α-羟化酶的表达。结节病患者支气管肺泡灌洗细胞中的1α-羟化酶mRNA水平比对照患者高5倍（10.8±3.6对2.2±1.4，P<0.003）。在所有研究患者中，支气管肺泡灌洗样本中的1α-羟化酶mRNA水平与肺泡淋巴细胞百分比（r = 0.83，P<0.005）、CD4/CD8比值（r = 0.77，P<0.02）、血清ACE水平（r = 0.58，P<0.05）、血清离子钙水平（r = 0.58，P<0.05）以及骨化三醇/25-羟维生素D3比值（r = 0.57，P<0.05）之间存在显著相关性。在结节病患者中，1α-羟化酶mRNA与肺泡淋巴细胞百分比之间也观察到显著相关性（r = 0.82，P<0.05）。