PRODUCTION OF 1,25-DIHYDROXYVITAMIN-D3 BY PULMONARY ALVEOLAR MACROPHAGES FROM PATIENTS WITH SARCOIDOSIS
PRODUCTION OF 1,25-DIHYDROXYVITAMIN-D3 BY PULMONARY ALVEOLAR MACROPHAGES FROM PATIENTS WITH SARCOIDOSIS
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DOI：
10.1111/j.1749-6632.1986.tb18535.x
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发表时间：
1986-06-06
影响因子：
5.2
通讯作者：
SHARMA, OP
中科院分区：
文献类型：
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作者：
ADAMS, JS;GACAD, MA;SHARMA, OP
1954年，Henneman et aI。是第一个提出结节病的高钙血症/高钙血症紊乱与内源性维生素d过量产生有关。他们的假设得到了钙平衡数据的支持，这些数据显示肠道钙过度吸收，以及历史证据表明，当皮肤暴露在更多的紫外线下时，结节病患者的高钙血症或高钙尿症在夏季加剧。然而，观察到结节病患者在维生素D治疗期间容易发生高钙血症4，这促使Anderson等人进行了研究。和其他研究人员提出，结节病患者对维生素D的敏感性是异常的。结节病中的钙代谢紊乱是由于终末器官对维生素D的敏感性增加，直到认识到在一些高钙尿和/或高钙血症的结节病患者中血清1,25 -二羟基维生素D (1,25 -(OH),-D)（甾醇激素的活性形式）水平升高。最近，在一名患有结节病的高钙血症、无肾男性患者中，报道了血清中125 -(OH) - d（一种仅在正常、未怀孕人类受试者肾脏中合成的代谢物）浓度升高。这些数据支持Henneman等人最初的假设，即结节病的高钙血症确实是维生素D中毒的一种形式，并进一步表明激素的来源存在于肾外部位。本报告中描述的实验指出，结节病患者的肺泡巨噬细胞（PAM）是该疾病中活性维生素D甾醇的合成来源，并将其代谢产物表征为1,25 -(OH),-D。
In 1954 Henneman et aI.'were the first to suggest that the hypercalcemic/hypercalciuric disturbance in sarcoidosis was related to the endogenous overproduction of vitamin D. Their postulate was supported by data on calcium balance that showed intestinal calcium hyperabsorption,'S2 and by historical evidence that showed exacerbation of hypercalcemia or hypercalciuria during summer months, when skin is exposed to more ultraviolet light: in patients with sarcoidosis. The observation that patients with sarcoidosis were susceptible to the development of hypercalcemia during treatment with vitamin D, 4 however, prompted Anderson et a/.* and other investigators'-'to propose that sensitivity to vitamin D in sarcoidosis was abnormal. The notion that the calcium metabolic disturbance in sarcoidosis resulted from increased end-organ sensitivity to vitamin D persisted until it was recognized that serum levels of 1, 25-dihydroxyvitamin D (1, 25-(OH),-D), the active form of the sterol hormone, were elevated in some sarcoidosis patients with hypercalciuria and/or hyper-~ alcemia.~~~ More recently, an elevated serum concentration of 1, 25-(OH),-D, a metabolite synthesized solely in the kidney in normal, nonpregnant human subjects," was reported in a hypercalcemic, anephric male patient with sarcoidosis." These data support the original postulate of Henneman et al. that the hypercalcemia of sarcoidosis is indeed a form of vitamin D intoxication and further suggest that the source of hormone exists at an extrarenal site. The experiments described in the present report point to the pulmonary alveolar macrophage (PAM) in patients with sarcoidosis as the synthetic source of an active vitamin D sterol in this disease and characterize the metabolite as 1, 25-(OH),-D,.