Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins

Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins
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DOI:
10.1016/s0092-8674(00)81032-6
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发表时间:
1996-02-23
期刊:
影响因子:
64.5
通讯作者:
Wagner, DD
Wagner, DD
中科院分区:
生物学1区
文献类型:
--
作者:
Frenette, PS;Mayadas, TN;Wagner, DD

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我们描述的表型小鼠缺乏内皮选择素后,连续消融的基因编码的P-和E-选择素。与在单一选择素基因缺陷的小鼠中观察到的相当温和的表型相反,双重缺陷的小鼠呈现极端的白细胞增多、升高的细胞因子水平和造血的改变。粒细胞生成在骨髓和脾脏中均增加,而红细胞生成部分转移至脾脏。炎症部位白细胞滚动的实际缺乏和低外渗使这些动物对机会性细菌感染易感,它们屈服于机会性细菌感染。我们的研究结果表明,内皮选择素的缺乏严重影响白细胞的稳态,并表明这两个选择素是一样重要的正常白细胞功能的白细胞β 2整合素。
We describe the phenotype of mice lacking both endothelial selectins after sequential ablation of the genes encoding P- and E-selectins. In contrast with the rather mild phenotypes observed in mice deficient in a single selectin gene, the doubly deficient mice present extreme leukocytosis, elevated cytokine levels, and alterations in hematopoiesis. Granulocytopoiesis is increased both in bone marrow and spleen, while erythropoiesis is partially translocated to the spleen. Virtual lack of leukocyte rolling and low extravasation at sites of inflammation make these animals susceptible to opportunistic bacterial infections, to which they succumb. Our results show that the absence of endothelial selectins severely affects leukocyte homeostasis and indicate that these two selectins are as important for normal leukocyte function as are the leukocyte beta 2 integrins.