Metabolism of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3 by blood derived macrophages from a patient with alveolar rhabdomyosarcoma during short-term culture and 1 alpha,25-dihydroxyvitamin D3 after long-term culture. 1991

M E Hayes, and D Bayley, and M Drayson, and A J Freemont, and J Denton, and M Davies, and E B Mawer
University Department of Medicine, Royal Infirmary, Manchester, England.

We have examined the ability of blood-derived monocytes and macrophages isolated from a patient with alveolar rhabdomyosarcoma and hypercalcaemia, to form 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) from 25-hydroxyvitamin D3 (25(OH)D3). Adherent monocyte-macrophage cells incubated with 25(OH)D3 over the initial 2 days in culture synthesized 1.9 pmol 24,25(OH)2D3/h/incubation (representing 0.63 pmol/h/10(6) cells), whereas macrophages synthesized 1.03 and 1.15 pmol 1 alpha,25(OH)2D3/h/incubation after 1 and 4 weeks in culture respectively. In a further experiment synthesis of 1 alpha,25(OH)2D3 by long-term cultured macrophages fell from 2.25 to 0.04 pmol/h/incubation following exposure to 10 nM 1 alpha,25(OH)2D3 for 7 days, whereas 24,25(OH)2D3 synthesis was induced (0.46 pmol/h/incubation). The vitamin D3 metabolites were identified by co-chromatography with authentic 24,25(OH)2D3 or 1 alpha,25(OH)2D3 in three different high-performance liquid chromatography systems. Serum 1 alpha,25(OH)2D3 in the patient was markedly suppressed at 5 pg/ml (normal 20-50 pg/ml) indicating that raised 1 alpha,25(OH)2D3 was not the cause of the hypercalcaemia, but rather, that raised calcium may have suppressed renal 1 alpha,25(OH)2D3 synthesis. Administration of APD (3-amino-1-hydroxypropylidine-1,1-bisphosphonate) corrected the hypercalcaemia in the patient suggesting that increased bone resorption was responsible for the raised calcium. The results of this study show for the first time that immature blood derived monocyte-macrophage cells can synthesize 24,25(OH)2D3 before they mature into macrophages able to synthesize 1 alpha,25(OH)2D3.

UI MeSH Term Description Entries
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D002112 Calcifediol The major circulating metabolite of VITAMIN D3. It is produced in the LIVER and is the best indicator of the body's vitamin D stores. It is effective in the treatment of RICKETS and OSTEOMALACIA, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. 25-Hydroxycholecalciferol,25-Hydroxyvitamin D 3,25-Hydroxycholecalciferol Monohydrate,25-Hydroxyvitamin D3,Calcidiol,Calcifediol Anhydrous,Calcifediol, (3 alpha,5Z,7E)-Isomer,Calcifediol, (3 beta,5E,7E)-Isomer,Calderol,Dedrogyl,Hidroferol,25 Hydroxycholecalciferol,25 Hydroxycholecalciferol Monohydrate,25 Hydroxyvitamin D 3,25 Hydroxyvitamin D3,Anhydrous, Calcifediol,Monohydrate, 25-Hydroxycholecalciferol
D002117 Calcitriol The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. 1 alpha,25-Dihydroxycholecalciferol,1 alpha,25-Dihydroxyvitamin D3,1, 25-(OH)2D3,1,25(OH)2D3,1,25-Dihydroxycholecalciferol,1,25-Dihydroxyvitamin D3,1 alpha, 25-dihydroxy-20-epi-Vitamin D3,1,25(OH)2-20epi-D3,1,25-dihydroxy-20-epi-Vitamin D3,20-epi-1alpha,25-dihydroxycholecaliferol,Bocatriol,Calcijex,Calcitriol KyraMed,Calcitriol-Nefro,Decostriol,MC-1288,MC1288,Osteotriol,Renatriol,Rocaltrol,Silkis,Sitriol,Soltriol,Tirocal,1 alpha,25 Dihydroxyvitamin D3,1,25 Dihydroxycholecalciferol,1,25 Dihydroxyvitamin D3,1,25 dihydroxy 20 epi Vitamin D3,Calcitriol Nefro,D3, 1 alpha,25-Dihydroxyvitamin,D3, 1,25-Dihydroxyvitamin,D3, 1,25-dihydroxy-20-epi-Vitamin,KyraMed, Calcitriol,MC 1288
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006934 Hypercalcemia Abnormally high level of calcium in the blood. Milk-Alkali Syndrome,Hypercalcemias,Milk Alkali Syndrome,Syndrome, Milk-Alkali
D012208 Rhabdomyosarcoma A malignant solid tumor arising from mesenchymal tissues which normally differentiate to form striated muscle. It can occur in a wide variety of sites. It is divided into four distinct types: pleomorphic, predominantly in male adults; alveolar (RHABDOMYOSARCOMA, ALVEOLAR), mainly in adolescents and young adults; embryonal (RHABDOMYOSARCOMA, EMBRYONAL), predominantly in infants and children; and botryoidal, also in young children. It is one of the most frequently occurring soft tissue sarcomas and the most common in children under 15. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p2186; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, pp1647-9) Rhabdomyosarcomas
D015650 24,25-Dihydroxyvitamin D 3 A physiologically active metabolite of VITAMIN D. The compound is involved in the regulation of calcium metabolism, alkaline phosphatase activity, and enhancing the calcemic effect of CALCITRIOL. 24,25-Dihydroxycholecalciferol,(24R)-24,25-Dihydroxyvitamin D3,24,25 Dihydroxyvitamin D3,24,25-Dihydroxyvitamin D 3, (3beta,5Z,7E,24R)-Isomer,24,25-Dihydroxyvitamin D3,24R,25-Dihydroxycholecalciferol,24,25 Dihydroxycholecalciferol,24,25 Dihydroxyvitamin D 3,24R,25 Dihydroxycholecalciferol,Dihydroxyvitamin D3, 24,25

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