Gainsford T, Willson T A, Metcalf D, Handman E, McFarlane C, Ng A, Nicola N A, Alexander W S, Hilton D J
Walter and Eliza Hall Institute for Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14564-8. doi: 10.1073/pnas.93.25.14564.
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 murine 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.
许多细胞因子通过血细胞生成素受体家族成员发挥其生物学效应。利用针对常见WSXWS基序的简并寡核苷酸，我们从人血细胞cDNA文库中克隆出了多种形式的受体，该受体最近被证明可结合肥胖激素瘦素。编码人瘦素受体长、短形式的mRNA在一系列人和小鼠造血器官中共同表达，并且这些组织中的一部分细胞在细胞表面结合瘦素。在小鼠Ba/F3和M1细胞系中的异位表达表明，瘦素受体的长形式而非短形式可分别发出增殖和分化信号。在小鼠或人骨髓细胞培养物中，人瘦素没有刺激细胞存活或增殖的能力，但它增强了小鼠腹腔巨噬细胞的细胞因子产生以及对利什曼原虫寄生虫的吞噬作用。我们的数据提供了证据，表明除了在脂肪调节中的作用外，瘦素还可能能够调节造血和巨噬细胞功能的某些方面。
