THE INDUCTION OF ACCELERATED THYMIC PROGRAMMED CELL-DEATH DURING POLYMICROBIAL SEPSIS - CONTROL BY CORTICOSTEROIDS BUT NOT TUMOR-NECROSIS-FACTOR
THE INDUCTION OF ACCELERATED THYMIC PROGRAMMED CELL-DEATH DURING POLYMICROBIAL SEPSIS - CONTROL BY CORTICOSTEROIDS BUT NOT TUMOR-NECROSIS-FACTOR
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DOI：
10.1097/00024382-199504000-00003
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发表时间：
1995-04-01
期刊：
影响因子：
3.1
通讯作者：
CHAUDRY, IH
中科院分区：
文献类型：
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作者：
AYALA, A;HERDON, CD;CHAUDRY, IH
胸腺程序性细胞死亡（PCD）或凋亡（A（O））在炎症过程中被多种压力源在体外（即糖皮质激素，糖皮质激素，肿瘤坏死因子（TNF），前类样子等）升高，但是很少或没有信息可用于有关其在多数型败血症中的存在。为了确定败血症发作后的胸腺中是否在胸腺中加速了PCD，在盲肠结扎和穿刺（CLP; CLP;诱导败血症）或Sham-sham-sham-sham-shem-sham-shem-hen小鼠中从1、4、12和24 h收集胸腺细胞。 CLP（假），并根据FACS分析（碘化丙啶染色）或通过基因组DNA碎裂的证据来评估胸腺细胞生存的细胞产量变化，增加了A（O）+细胞。结果表明，在CLP后1小时，这些参数中的任何一个都没有明显变化。然而，到CLP 4小时，A（O）+胸腺细胞的百分比增加了，化粪池基因组DNA表现出痕量的片段化。这些变化通过12和24小时在化脓性动物细胞中增加。或者，直到12小时，胸腺活细胞产量才显着降低。在所有时间点，在化脓性小鼠血液中也检测到全身介质，皮质酮和TNF的明显变化。为了确定这两种药物对此处所见的加速PCD的贡献，将小鼠随机分配以接收RU-38486（11 beta- [p-（dimethylamino）苯基] -17 beta-hydroxy-17-17-17-17-17-17-17-17-17- （1-propopynyl）Estra-4,9-Dien-3-One（米非司酮），类固醇受体阻滞剂），聚乙烯乙二醇（PEG） - （RSTNF-R1）（RSTNF-R1）（2）（TNF抑制剂）。 RU-38486未见败血症（CLP）诱导的活胸腺细胞产量下降，而是存在于PEG-（RSTNF-R1）（2）处理的小鼠中。此外，与PEG-（RSTNF-R1）（2）不同，RU-38486明显降低了A（O）+以及DNA片段化程度的细胞百分比。因此，脓肿中败血症诱导的PCD不是对TNF的响应，而是在败血症发作后释放的皮质糖蛋白酶在体内受到控制。
Thymic programmed cell death (PCD) or apoptosis (A(o)) is elevated during inflammation by a variety of stressors in vitro (i.e., glucocorticoids, tumor necrosis factor (TNF), prostanoids, etc.), however, little or no information is available concerning its presence in polymicrobial sepsis. To establish whether or not PCD is accelerated in the thymus following the onset of sepsis, thymocytes were harvested from C3H/HeN mice at 1, 4, 12, and 24 h following cecal ligation and puncture (CLP; to induce sepsis) or Sham-CLP (Sham), and assessed for changes in thymocyte viable cell yield, increased A(o)+ cells based on FACS analysis (propidium iodide staining) or by evidence of fragmentation of the genomic DNA. The results indicate that at 1 h post-CLP there were no marked changes in any of these parameters. However, by 4 h post-CLP the percentage of A(o)+ thymocytes increased and the septic mouse genomic DNA exhibited trace amounts of fragmentation. These changes increased in the septic animals cells through both 12 and 24 h. Alternatively, thymic viable cell yield did not significantly decrease until 12 h. Marked changes in systemic mediators, corticosterone and TNF, were also detected in septic mouse blood at all time points. In an effort to determine the contribution of these two agents to the induction of the accelerated PCD seen here, mice were randomized to receive either RU-38486 (11 beta-[p-(dimethylamino)phenyl]-17 beta-hydroxy-17- (1-propynyl)estra-4,9-dien-3-one (Mifepristone); a steroid receptor blocker), polyethylene glycol (PEG)-(rsTNF-R1)(2) (a TNF inhibitor) immediately following CLP. The decline in viable thymocyte cell yield induced by sepsis (CLP) was not seen with RU-38486, but was present in PEG-(rsTNF-R1)(2)-treated mice. Furthermore, RU-38486, unlike PEG-(rsTNF-R1)(2), treatment markedly decreased the percentage of cells which were A(o)+ as well as the extent of DNA fragmentation. Thus, sepsis-induced PCD in the thymus is not a response to TNF but appears to be controlled in vivo by corticosteriods released after the onset of sepsis.