Shirai M, Sato A, Chida K
Department of Internal Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan.
Nihon Kyobu Shikkan Gakkai Zasshi. 1991 Jul;29(7):836-43.
It is supposed that the effects of glucocorticoid on target cells are mediated by glucocorticoid receptors. Recent investigations have demonstrated that changes in the composition and function of immune cells in bronchoalveolar lavage (BAL) cells of patients with immunological lung diseases are associated with the intensity of alveolar septal inflammation, or indicate steroid responsiveness. In order to clarify the physiologic changes of glucocorticoid receptor (GR) we measured the GR content of BAL cells obtained from rabbits with various conditions of the host (aging, immunological activation, malnutrition and pretreatment with prednisolone). The specific binding to GR was carried out by incubating BAL cells with 1, 2, 4, 10, 20, 40 nM 3H-prednisolone in the presence or absence of 1.0 x 10(-6) M unlabeled prednisolone. BAL cells from rabbits of various ages exhibited age-dependent reduction of GR content. There were striking differences of GR content in BAL cells from normal and BCG-vaccinated rabbits. The former yielded 3124 +/- 365 binding sites per cell, whereas activated BAL cells showed considerably higher values (6807 +/- 766). Chronological changes in GR content in BAL cells were also observed in normal rabbits pretreated with intravenous injection of prednisolone (2 mg/kg). The GR content was lowest at 3 hours after administration, reaching a peak at two days and then returned to control level. As for nutritional modulation, GR content tended to increase in the initial phase of fasting (days 4 to 8), and then decreased after day 12. In contrast, there were no significant changes in dissociation constants among BAL cells from animals in normal, immunologically activated and malnourished conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
一般认为,糖皮质激素对靶细胞的作用是由糖皮质激素受体介导的。最近的研究表明,免疫性肺疾病患者支气管肺泡灌洗(BAL)细胞中免疫细胞的组成和功能变化与肺泡间隔炎症的强度相关,或表明对类固醇的反应性。为了阐明糖皮质激素受体(GR)的生理变化,我们测量了从处于各种宿主条件(衰老、免疫激活、营养不良和用泼尼松龙预处理)的兔子获得的BAL细胞中的GR含量。通过在存在或不存在1.0×10(-6)M未标记泼尼松龙的情况下,将BAL细胞与1、2、4、10、20、40 nM 3H-泼尼松龙孵育来进行与GR的特异性结合。不同年龄兔子的BAL细胞显示出GR含量的年龄依赖性降低。正常和卡介苗接种兔子的BAL细胞中GR含量存在显著差异。前者每个细胞产生3124±365个结合位点,而活化的BAL细胞显示出相当高的值(6807±766)。在用泼尼松龙(2mg/kg)静脉注射预处理的正常兔子中也观察到BAL细胞中GR含量的时间变化。给药后3小时GR含量最低,两天时达到峰值,然后恢复到对照水平。至于营养调节,GR含量在禁食初期(第4至8天)趋于增加,然后在第12天后下降。相比之下,正常、免疫激活和营养不良条件下动物的BAL细胞之间的解离常数没有显著变化。(摘要截断于250字)