Over-expression of Bcl-2 provides protection in septic mice by a trans effect
Over-expression of Bcl-2 provides protection in septic mice by a trans effect
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DOI：
10.4049/jimmunol.171.6.3136
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发表时间：
2003-09-15
影响因子：
4.4
通讯作者：
Winn, RK
中科院分区：
文献类型：
--
作者：
Iwata, A;Stevenson, VM;Winn, RK
在盲肠结扎和穿刺（CLP）后，将在人MRP 8启动子（hMRP 8-Bcl-2）控制下的髓样细胞中或在Emu启动子（Emu-Bcl-2）控制下的T淋巴细胞中过表达B细胞白血病/淋巴瘤（Bel）-2的转基因小鼠与C57 BL/6对照小鼠进行比较。hMRP 8-Bcl-2和对照小鼠之间的结果存在显著差异，hMRP 8-Bcl-2小鼠的存活率为100%，对照小鼠的存活率为25%。在单独的实验中，Emu-Bcl-2和对照小鼠之间存在显著差异，分别为87.5%和22.2%的存活率。将来自hMRP 8-Bcl-2或C57 BL/6小鼠的CD 11b阳性骨髓细胞连续转移至经受CLP的C57 BL/6小鼠，分别导致100%和0%的存活。将来自hMRP 8-Bcl-2或C57 BL/6小鼠的CD 11 b阳性细胞连续转移至经受CLP的Rag-1（-/-）小鼠（无成熟T或B细胞），分别导致87.5%和12.5%的存活率。CLP后24 h，hMRP 8-Bcl-2小鼠与C57 BL/6小鼠相比，腹膜中的中性粒细胞显著更多，细菌显著更少。这些实验表明Bcl-2过表达在CLP中具有保护作用，并且这种保护作用不依赖于淋巴细胞。我们认为Bcl-2在T细胞或骨髓细胞中的过表达诱导了一种分子的释放，这种分子可以防止CLP后的死亡。
Transgenic mice that over-express B cell leukemia/lymphomas (Bel)-2 in myeloid cells under control of the human MRP8 promoter (hMRP8-Bcl-2) or in T lymphocytes under the Emu promoter (Emu-Bcl-2) were compared with C57BL/6 control mice following cecal ligation and puncture (CLP). There was a significant difference in outcome between the hMRP8-Bcl-2 and control mice with 100% survival in the hMRP8-Bcl-2 mice vs 25% survival in the control mice. In separate experiments there was a significant difference between Emu-Bcl-2 and control mice with 87.5 and 22.2% survival, respectively. Adoptive transfer of CD11b-positive bone marrow cells from hMRP8-Bcl-2 or C57BL/6 mice to C57BL/6 mice subjected to CLP resulted in 100 and 0% survival, respectively. Adoptive transfer of CD11b-positive cells from either hMRP8-Bcl-2 or C57BL/6 mice to Rag-1(-/-) mice (no mature T or B cells) subjected to CLP resulted in survival of 87.5 and 12.5%, respectively. The hMRP8-Bcl-2 mice had significantly more neutrophils and fewer bacteria in the peritoneum compared with C57BL/6 mice 24 h after CLP. These experiments show that Bcl-2 over-expression is protective in CLP and that protection is independent of lymphocytes. We propose that overexpression of Bcl-2 in T cells or myeloid cells induce release of a molecule(s) that protects against death following CLP.