Biomaterial Database

25-Hydroxyvitamin D3 metabolism by human T-lymphotropic virus-transformed lymphocytes. 1987

H Reichel, and H P Koeffler, and A W Norman

Production of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] by human T-lymphotropic virus-I (HTLV-I)-infected lymphocytes may be the cause of the hypercalcemia frequently found in HTLV-I-associated adult T-cell lymphoma/leukemia. We examined three HTLV-I-transformed lymphocyte cell lines, two HTLV-II-transformed lymphocyte cell lines, and six HTLV-negative B and T-lymphocyte leukemia cell lines for metabolism of 25-hydroxyvitamin D3 (25OHD3). One HTLV-I-positive cell line, designated S-LB1, converted the substrate 25OH-[3H]D3 to several more polar metabolites, which were identified by high performance liquid chromatographic analysis as putative 1,25-(OH)2D3, 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3], and 1,24,25-trihydroxyvitamin D3 [1,24,25-(OH)3D3]. The other cell lines gave no evidence of 25OH-[3H]D3 metabolism. Likewise, phytohemagglutinin-stimulated normal human lymphocytes did not metabolize 25OH-[3H]D3. The characteristics of 25OHD3 metabolism by S-LB1 cells were investigated in more detail. Kinetic studies revealed average Km values of 92 and 383 nM for 25OHD3 1-hydroxylase and 24-hydroxylase, respectively. Time-course studies showed that both 1,25-(OH)2-[3H]D3 and 24,25-(OH)2-[3H]D3 were further metabolized by S-LB1 cells to more polar compounds [primarily 1,24,25-(OH)3D3] and to compounds from which part of the side-chain had been cleaved. Exogenous 1,25-(OH)2D3 (1) inhibited endogenous 1,25-(OH)2D3 production, (2) stimulated 24,25-(OH)2D3 production, and (3) stimulated production of compounds more polar than 1,25-(OH)2D3. Bovine PTH-(1-34) had no effect on 25OH-[3H]D3 metabolism by S-LB1 cells. Our results indicate that the 25OH-[3H]D3-metabolizing system of cultured HTLV-I-transformed S-LB1 lymphocytes is similar but not identical to that of kidney cell culture systems. It appears, however, that infection of lymphocytes with HTLV does not uniformly result in acquisition of the competence to metabolize 25OHD3.

UI	MeSH Term	Description	Entries
D008214	Lymphocytes	White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.	Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
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
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D002472	Cell Transformation, Viral	An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus.	Transformation, Viral Cell,Viral Cell Transformation,Cell Transformations, Viral,Transformations, Viral Cell,Viral Cell Transformations
D006800	Deltaretrovirus Infections	Infections caused by the HTLV or BLV deltaretroviruses. They include human T-cell leukemia-lymphoma (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED).	BLV Infections,HTLV Infections,HTLV-BLV Infections,BLV Infection,Deltaretrovirus Infection,HTLV BLV Infections,HTLV Infection,HTLV-BLV Infection,Infection, Deltaretrovirus,Infections, Deltaretrovirus
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
D001402	B-Lymphocytes	Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.	B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D013601	T-Lymphocytes	Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.	T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D017977	Deltaretrovirus	A genus in the family RETROVIRIDAE consisting of exogenous horizontally-transmitted viruses found in a few groups of mammals. Infections caused by these viruses include human B- or adult T-cell leukemia/lymphoma (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED), and bovine leukemia (ENZOOTIC BOVINE LEUKOSIS). The type species is LEUKEMIA VIRUS, BOVINE.	BLV-HTLV Viruses,HTLV Viruses,HTLV-BLV Viruses,Human T-Cell Leukemia Viruses,Human T-Cell Leukemia-Lymphoma Viruses,Leukemia Viruses, Human T-Cell,T-Cell Leukemia Viruses, Human,Human T Cell Leukemia Lymphoma Viruses,Human T Cell Leukemia Viruses,Leukemia Viruses, Human T Cell,T Cell Leukemia Viruses, Human,BLV HTLV Viruses,HTLV BLV Viruses