Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part II: Increased P-glycoprotein activity in lymphocytes from systemic lupus erythematosus patients might affect steroid requirements for disease control.
Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part II: Increased P-glycoprotein activity in lymphocytes from systemic lupus erythematosus patients might affect steroid requirements for disease control.
复制标题
风湿性自身免疫性疾病中的多药耐药性 1 (MDR-1)。
DOI：
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发表时间：
2000
期刊：
影响因子：
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通讯作者：
Luis Llorente
中科院分区：
文献类型：
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作者：
A. Díaz;Y. Richaud;C. AlvaradodelaBarrera;J. Jakez;A. Ruiz;Luis Llorente
背景
被称为P-糖蛋白的膜糖蛋白的过度表达已经在多种正常和肿瘤细胞中被广泛观察到。P-糖蛋白是一种泵分子，可将疏水性药物（包括类固醇）和毒素转运到细胞外，从而抑制其治疗或毒性作用。编码P-糖蛋白的基因被命名为多药耐药-1（MDR-1）。
目的
探讨系统性红斑狼疮患者淋巴细胞和单核细胞P-糖蛋白的功能活性。
方法
对30例系统性红斑狼疮患者和20例健康对照者进行了研究。将通过梯度离心分离的外周血单核细胞在柔红霉素（一种由P-糖蛋白挤出的荧光药物）的存在下在37 ℃或4 ℃下孵育30 min。然后使用流式细胞术分析P-糖蛋白活性。结果表示为具有高P-糖蛋白活性的淋巴细胞或单核细胞的百分比（即，低荧光）。
结果
淋巴细胞和单核细胞的平均荧光值在患者和健康对照之间相当。然而，由于我们的方法允许在单细胞水平上测量P-糖蛋白功能，我们能够表明患者中具有高P-糖蛋白活性的淋巴细胞的平均百分比（11.51% +/- 14.3%）与健康对照组（0.71% +/- 0.57%）相比有所增加（P < 0.05）。此外，P-糖蛋白活性在临床缓解患者中低于活动性疾病患者。
结论
我们的结果表明P-糖蛋白功能可能影响系统性红斑狼疮对糖皮质激素的需求。
BACKGROUND
Over-expression of the membrane glycoprotein called P-glycoprotein has been widely observed in a variety of both normal and neoplastic cells. P-glycoprotein is a pump molecule that transports hydrophobic drugs (including steroids) and toxins outside the cells, thus inhibiting their therapeutic or toxic effects. The gene encoding P-glycoprotein is named multidrug resistance-1 (MDR-1).
OBJECTIVE
To evaluate the functional activity of P-glycoprotein in lymphocytes and monocytes from patients with systemic lupus erythematosus.
METHODS
30 systemic lupus erythematosus patients and 20 healthy controls were studied. Peripheral blood mononuclear cells isolated by gradient centrifugation were incubated in the presence of daunorubicin (a fluorescent drug extruded by P-glycoprotein) at 37 degrees C or 4 degrees C for 30 min. P-glycoprotein activity was then analyzed using flow cytometry. Results were expressed as the percentage of lymphocytes or monocytes with high P-glycoprotein activity (i.e., low fluorescence).
RESULTS
Mean fluorescence values for lymphocytes and monocytes were comparable between patients and healthy controls. However, because our method allowed to measure P-glycoprotein function at the single-cell level, we were able to show that the mean percentage of lymphocytes with high P-glycoprotein activity was increased in the patients (11.51% +/- 14.3%) as compared to the healthy controls (0.71% +/- 0.57%) (P < 0.05). Moreover, P-glycoprotein activity was lower in the patients in clinical remission than in those with active disease.
CONCLUSIONS
Our results suggest that P-glycoprotein function might affect glucocorticoid requirements in systemic lupus erythematosus.