Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells

Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells
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DOI:
10.1073/pnas.93.25.14564
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发表时间:
1996-12-10
影响因子:
11.1
通讯作者:
Hilton, DJ
Hilton, DJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gainsford, T;Willson, TA;Hilton, DJ

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许多细胞因子通过造血素受体家族的成员发挥其生物学效应,利用简并的寡核苷酸结合常见的WSXWS基序,我们已经从人造血细胞cDNA文库中克隆了各种形式的受体,最近被证明与肥胖激素结合,编码长形式和短形式的人瘦素受体的mRNAs在人和海洋的一系列造血器官中共表达,并且这些组织中的一组细胞与瘦素结合在细胞表面,在小鼠的BA/F3和M1细胞系中的异位表达表明,长的而不是短的形式的瘦素受体可以分别信号增殖和分化。在小鼠或人骨髓细胞培养中,人瘦素没有刺激细胞存活或增殖的能力,但它能促进小鼠腹腔巨噬细胞对利什曼原虫的吞噬和细胞因子的产生。我们的数据提供的证据表明,瘦素除了在脂肪调节中的作用外,还可能能够调节造血和巨噬细胞功能的各个方面。
Many cytokines exert their biological effect through members of the hemopoietin receptor family, Using degenerate oligonucleotides to the common WSXWS motif, we have cloned from human hemopoietic cell cDNA libraries various forms of the receptor that was recently shown to bind the obesity hormone, leptin, mRNAs encoding long and short forms of the human leptin receptor were found to be coexpressed in a range of human and marine hemopoietic organs, and a subset of cells from these tissues bound leptin at the cell surface, Ectopic expression in murine Ba/F3 and M1 cell lines revealed that the long, but not the short, form of the leptin receptor can signal proliferation and differentiation, respectively. In cultures of murine or human marrow cells, human leptin exhibited no capacity to stimulate cell survival or proliferation, but it enhanced cytokine production and phagocytosis of Leishmania parasites by murine peritoneal macrophages. Our data provide evidence that, in addition to its role in fat regulation, leptin may also be able to regulate aspects of hemopoiesis and macrophage function.