Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production.
Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production.
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作者：
败血症每年在美国造成20多万人死亡；迫切需要更好的治疗方法。在盲肠结扎和穿孔诱导脓毒症之前或之后不久，给小鼠注射骨髓基质细胞(BMSCs-也称为间充质干细胞)，可以降低死亡率并改善器官功能。去除巨噬细胞或用白介素10(IL-10)或IL-10受体特异性抗体预处理可消除骨髓间充质干细胞的有益作用。来自败血症肺的单核细胞和/或巨噬细胞在接受骨髓间充质干细胞治疗的小鼠与未治疗的小鼠相比，产生更多的IL-10。脂多糖(LPS)刺激的巨噬细胞在与BMSCs共同培养时产生更多的IL-10，但如果BMSCs缺乏编码Toll样受体4、髓系分化主要反应基因-88、肿瘤坏死因子受体-1a或环氧合酶-2的基因，这种作用就会消失。我们的结果表明，骨髓间充质干细胞(由内毒素或肿瘤坏死因子-α激活)通过释放前列腺素E2，通过前列腺素EP2和EP4受体作用于巨噬细胞，从而对巨噬细胞进行重新编程。由于BMSCs已经成功地移植给人类，而且可以很容易地培养，并且可能在没有人类白细胞抗原匹配的情况下使用，我们建议培养的、库中的人BMSCs可能在治疗高危患者组的脓毒症方面有效。
Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs—also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes and/or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated macrophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2. Our results suggest that BMSCs (activated by LPS or TNF-α) reprogram macrophages by releasing prostaglandin E2 that acts on the macrophages through the prostaglandin EP2 and EP4 receptors. Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups.
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影响因子：
--
作者：
HERNANDEZ, LA;GRISHAM, MB;GRANGER, DN
通讯作者：
GRANGER, DN
DOI：
10.1006/bbrc.1996.1112
发表时间：
1996-07-25
影响因子：
3.1
作者：
Imai, Y;Ibata, I;Kohsaka, S
通讯作者：
Kohsaka, S
影响因子：
20.3
作者：
Aggarwal, S;Pittenger, MF
通讯作者：
Pittenger, MF
影响因子：
3.9
作者：
Bal-Price, A;Gartlon, J;Brown, GC
通讯作者：
Brown, GC
影响因子：
20.3
作者：
Corcione, A;Benvenuto, F;Uccelli, A
通讯作者：
Uccelli, A