Metabolism of 25-hydroxyvitamin D3 by cultured pulmonary alveolar macrophages in sarcoidosis.
Metabolism of [3H]25-hydroxyvitamin D3(25-OH-D3) was studied in primary cultures of pulmonary alveolar macrophages (PAM) from seven patients with sarcoidosis and two patients with idiopathic pulmonary fibrosis. Production of a [3H]1,25-dihydroxyvitamin D3 (1,25-[OH]2-D3)-like metabolite of [3H]25-OH-D3 was detected in lipid extracts of cells from five patients with sarcoidosis. Synthesis of this compound in vitro was limited to viable PAM and was greatest in cells derived from a patient with hypercalcemia and an elevated serum concentration of 1,25-dihydroxyvitamin D. The tritiated PAM metabolite coeluted with authentic 1,25-(OH)2-D3 in three different solvent systems on straight-phase high performance liquid chromatography (HPLC) and demonstrated binding to extracted receptor for 1,25-(OH)2-D3, which was identical to that of commercially available [3H]1,25-(OH)2-D3 of comparable specific activity. Incubation of PAM with high concentrations of 25-OH-D3 resulted in production of an unlabeled metabolite that co-chromatographed with the 3H-PAM metabolite on HPLC and that was bound with high affinity by both the specific receptor for 1,25-(OH)2-D3 and antiserum to 1,25-(OH)2-D3.
D002112:Calcifediol / Q000378:metabolism*; D002117:Calcitriol / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D008171:Lung Diseases / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology*; D011658:Pulmonary Fibrosis / Q000378:metabolism; D012507:Sarcoidosis / Q000378:metabolism*
D002117:Calcitriol; D002112:Calcifediol