VITAMIN D METABOLISM BY T CELL LYMPHOCYTES

该项目的目的是描述维生素D的代谢 通过T细胞淋巴细胞在体外，特别注意生产 1，25-二羟维生素D（1，25（OH）2D），最活跃的代谢产物， 维生素D. 主要研究者的初步结果 实验室表明HTLV转化脐带血淋巴细胞具有 将25（OH）D转化为极性更强的代谢物的能力， 使用两种独立的高性能液体的正宗1，25（OH）2D 色谱系统和刺激骨吸收体外。 通过气相色谱/质谱法鉴别该代谢产物为1，25（OH）2D 光谱分析表明，这些转化的淋巴细胞 1-α-羟化酶活性。 由于1，25（OH）2D是一种有效的刺激剂， 骨细胞骨吸收，1，25（OH）2D或其他的产生增加 淋巴瘤细胞的维生素D代谢产物可能在发病机制中起作用 骨吸收和高钙血症的增加， 在这种疾病中。 因此，本研究的目的是使用HTLV转化的 淋巴细胞作为体外模型，研究维生素D的代谢， 淋巴细胞，以便： 1.表征HTLV产生的维生素D代谢产物 转化的T淋巴细胞，特别注意产生 1，25（OH）2D。 2.检查外周淋巴细胞对维生素D的代谢 淋巴细胞异常的其他疾病状态患者 功能和改变骨和矿物质代谢。 3.确定活化的正常淋巴细胞是否具有1-α-羟化酶 活动 4.表征正常和异常中的1-α-羟化酶活性 淋巴细胞，看看它是否受到相同的因素调节， 肾1-α-羟化酶活性。 这些研究将决定是否有能力生产 1，25（OH）2D是所有活化淋巴细胞的一般性质，或者是一种 HTLV病毒感染的淋巴细胞的独特性质。 此外，委员会认为， 该1-α-羟化酶活性的表征和 调节淋巴细胞1-α-羟化酶活性的那些因子将 提供有关控制维生素D的因素的重要信息 在正常个体和疾病状态中的代谢， 骨骼和矿物质代谢异常。 这些结果也将形成 研究的基础，旨在阐明负责的分子机制 用于激活淋巴细胞中的1-α-羟化酶活性。

The purpose of this project is to characterize the metabolism of vitamin D by T-cell lymphocytes in vitro with particular attention to the production of 1,25-dihydroxyvitamin D (1,25(OH)2D), the most active metabolite of vitamin D. Preliminary results from the Principal Investigator's laboratory indicate that HTLV-transformed cord blood lymphocytes have the capacity to convert 25(OH)D to a more polar metabolite which coelutes with authentic 1,25(OH)2D using two separate high performance liquid chromatography systems and stimulates bone resorption in vitro. Identification of this metabolite as 1,25(OH)2D by gas chromatography/mass spectrometry suggest that these transformed lymphocytes have 1-alpha-hydroxylase activity. Since 1,25(OH)2D is a potent stimulator of osteoclastic bone resorption, increased production of 1,25(OH)2D or other vitamin D metabolites by lymphoma cells may play a role in the pathogenesis of the increased osteoclastic bone resorption and hypercalcemia which occur in this disease. Accordingly, the purpose of this study is to use HTLV-transformed lymphocytes as an in vitro model to study the metabolism of vitamin D by lymphocytes in order to: 1. Characterize the metabolites of vitamin D which are produced by HTLV transformed T-lymphocytes with particular attention to the production of 1,25(OH)2D. 2. Examine the metabolism of vitamin D by peripheral lymphocytes in patients with other disease states characterized by abnormal lymphocyte function and altered bone and mineral metabolism. 3. Determine if activated normal lymphocytes have 1-alpha-hydroxylase activity. 4. Characterize the 1-alpha-hydroxylase activity in normal and abnormal lymphocytes to see if it is regulated by the same factors which regulate renal 1-alpha-hydroxylase activity. These studies will determine whether or not the ability to produce 1,25(OH)2D is a general property of all activated lymphocytes or is a unique property of lymphocytes infected with the HTLV virus. Moreover, characterization of this 1-alpha-hydroxylase activity and identification of those factors which regulate lymphocyte 1-alpha-hydroxylase activity will provide important information concerning factors that control vitamin D metabolism both in normal individuals and disease states characterized by abnormal bone and mineral metabolism. These results will also form the basis of studies designed to elucidate the molecular mechanisms responsible for the activation of 1-alpha-hydroxylase activity in lymphocytes.