Dréau D, Foster M, Morton D S, Fowler N, Kinney K, Sonnenfeld G
Department of General Surgery Research, Carolinas Medical Center, 1000, Blythe Boulevard, PO Box 32861, Charlotte, NC 28232, USA.
Physiol Behav. 2000 Sep 15;70(5):513-20. doi: 10.1016/s0031-9384(00)00296-1.
Using 2-deoxy-D-glucose (2-DG)-induced stress, our laboratory has developed studies to define stress effects on immune responses. Here, we report effects of increasing doses of 2-DG on the immune response of BALB/c, C57BL/6 and BDF(1) mice 2 h after three injections of 0 to 2000 mg/kg of 2-DG. Female 4- to 5-week-old mice were euthanized and blood and spleens were collected. A suspension of partially purified mature T splenocytes was obtained by negative selection using J11.d2 antibodies. Glucose and corticosterone levels were measured in the plasma of each mouse. Splenocyte and mature T splenocyte suspensions were tested in in vitro proliferation assays with or without concanavalin A. Splenocytes were analyzed for the following cell-surface markers: CD3, TCR alpha/beta, CD4, CD8 and major histocompatibility complex (MHC) Class II. Significant increases in blood glucose levels were observed in C57BL/6 and BALB/c strains with the highest 2-DG dose (p<0.05). Corticosterone levels were higher in BDF(1) mice and C57BL/6 mice following the administration of 1000 and 2000 mg/kg of 2-DG, respectively (p<0.01). In vitro proliferation of mature T splenocytes in the presence of concanavalin A was decreased in BDF(1) (p<0.05) but not in BALB/c and C57BL/6 mice. In addition, in BDF(1) mice the decrease was highly correlated with an increase of CD3+ and TCR alpha/beta+ cells in the spleen. These results demonstrated high variability in the response of different mouse strains to 2-DG-induced stress.
利用2-脱氧-D-葡萄糖(2-DG)诱导的应激,我们实验室开展了多项研究来确定应激对免疫反应的影响。在此,我们报告在三次注射0至2000 mg/kg的2-DG后2小时,递增剂量的2-DG对BALB/c、C57BL/6和BDF(1)小鼠免疫反应的影响。对4至5周龄的雌性小鼠实施安乐死后,采集血液和脾脏。通过使用J11.d2抗体进行阴性选择获得部分纯化的成熟T脾细胞悬液。检测每只小鼠血浆中的葡萄糖和皮质酮水平。在有或无伴刀豆球蛋白A的情况下,对脾细胞悬液和成熟T脾细胞悬液进行体外增殖试验。分析脾细胞的以下细胞表面标志物:CD3、TCRα/β、CD4、CD8和主要组织相容性复合体(MHC)II类。在2-DG剂量最高时,C57BL/6和BALB/c品系的血糖水平显著升高(p<0.05)。分别给予1000和2000 mg/kg的2-DG后,BDF(1)小鼠和C57BL/6小鼠的皮质酮水平升高(p<0.01)。在伴刀豆球蛋白A存在的情况下,BDF(1)小鼠成熟T脾细胞的体外增殖减少(p<0.05),但BALB/c和C57BL/6小鼠未出现这种情况。此外,在BDF(1)小鼠中,这种减少与脾脏中CD3+和TCRα/β+细胞的增加高度相关。这些结果表明不同小鼠品系对2-DG诱导应激的反应存在高度变异性。