Accelerated destruction of erythrocytes in Tie2 promoter-driven STAT3 conditional knockout mice.
Accelerated destruction of erythrocytes in Tie2 promoter-driven STAT3 conditional knockout mice.
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DOI：
10.1016/j.lfs.2013.07.025
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发表时间：
2013-09
期刊：
影响因子：
6.1
通讯作者：
N. Ohkubo;Yoji Suzuki;M. Aoto;J. Yamanouchi;S. Hirakawa;M. Yasukawa;N. Mitsuda
中科院分区：
文献类型：
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作者：
N. Ohkubo;Yoji Suzuki;M. Aoto;J. Yamanouchi;S. Hirakawa;M. Yasukawa;N. Mitsuda
目的STAT3是巨噬细胞活化和分化的关键调节因子。但目前尚不清楚STAT3的缺失是否会激活巨噬细胞，通过吞噬作用破坏红细胞。本研究利用Tie2启动子驱动的Cre重组酶转基因小鼠与STAT3小鼠杂交，获得了STAT3条件性基因敲除小鼠，明确了STAT3在巨噬细胞的形成和激活过程中起着重要的作用。为了探索小鼠的红细胞生成功能，我们通过给小鼠腹腔注射苯肼来使它们发生短暂的溶血性贫血。用扫描电子显微镜和渗透耐量试验检测红细胞脆性。关键发现条件性基因敲除小鼠有轻度的中性粒细胞贫血。与野生型对照相比，它们还表现出更高的乳酸脱氢酶、铁蛋白和促红细胞生成素浓度，更多的网织红细胞数量，以及更短的红细胞寿命。这些数据表明，在STAT3条件性基因敲除小鼠中，红细胞的破坏和二次造血加速。它的出现并不是由于红细胞的易碎性。少数条件性基因敲除小鼠突然出现急性重度贫血、体温升高和脾肿大，并在贫血发病后2周内死亡。本研究为STAT3在脾内常驻巨噬细胞破坏红细胞过程中发挥关键作用提供了证据。
AimsSTAT3 is a key modulator of activation and differentiation of macrophages. But it is still unknown if deficiency of STAT3 activates macrophages to destroy erythrocytes by phagocytosis. We generatedSTAT3conditional knockout mice by crossing floxedSTAT3mice withTie2promoter-driven Cre-recombinase transgenic mice and clarified that Stat3 plays a critical role in the formation and activation of macrophages.Main methodsBlood cell count, reticulocyte count, serum lactate dehydrogenase, erythropoietin, iron and ferritin concentration, and life span of the erythrocytes inTie2promoter-drivenSTAT3conditional knockout mice were analyzed. To explore the erythropoietic function of the mice, we subjected them to brief hemolytic anemia by injecting them intraperitoneally with phenylhydrazine. The fragility of erythrocytes was examined by scanning electron microscopy and osmotic tolerance test.Key findingsThe conditional knockout mice had mild normocytic anemia. They also displayed higher lactate dehydrogenase, ferritin and erythropoietin concentration, higher reticulocyte count, and a shorter lifespan of erythrocytes compared with wild-type controls. These data suggest that destruction of erythrocytes and secondary blood formation were accelerated in theSTAT3conditional knockout mice. It didn't appear due to the fragility of erythrocytes. A few of the conditional knockout mice suddenly developed acute severe anemia, high body temperature and massive splenomegaly, and died within 2 weeks after the onset of anemia.SignificanceThis study provided evidence that STAT3 have a critical role in the destruction of erythrocytes by resident macrophages in the spleen.