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

PURPOSE: To demonstrate expression of the 25-hydroxyvitamin D3 1 alpha -hyd roxylase (1 alpha -hydroxylase) gene in human alveolar macrophages and meas ure the correlations among the 1 alpha -hydroxylase mRNA level, the activit y 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 lava ge. Levels of 1 alpha -hydroxylase mRNA were measured by semiquantitative p olymerase chain reaction amplification. We measured serum levels of calcium , ionized calcium, parathyroid hormone, calcitriol (1,25-dihydroxyvitamin D 3), and 25-hydroxyvitamin D3 to evaluate calcium metabolism. To estimate th e 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 hu man alveolar macrophages. The 1 alpha -hydroxylase mRNA levels in bronchoal veolar lavage cells were fivefold higher in sarcoidosis patients than in co ntrol patients (10.8 +/- 3.6 vs. 2.2 +/- 1.4, P <0.003). Among all patients studied, there were significant correlations between the la-hydroxylase mR NA level in bronchoalveolar lavage samples and the percentage of alveolar l ymphocytes (r = 0.83, P <0.005), the CD4/CD8 ratio (r = 0.77, P <0.02), ser um 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 be tween 1 alpha -hydroxylase mRNA and the percentage of alveolar lymphocytes (r = 0.82, P <0.05). CONCLUSION: There is a correlation between la-hydroxylase gene expression i n alveolar macrophages with the activity of sarcoidosis and its associated disturbances in calcium metabolism. Am J Med. 2001;110:687-693. (C) 2001 by Excerpta Medica, Inc.