Spiegel Asaf, Shivtiel Shoham, Kalinkovich Alexander, Ludin Aya, Netzer Neta, Goichberg Polina, Azaria Yaara, Resnick Igor, Hardan Izhar, Ben-Hur Herzel, Nagler Arnon, Rubinstein Menachem, Lapidot Tsvee
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Nat Immunol. 2007 Oct;8(10):1123-31. doi: 10.1038/ni1509. Epub 2007 Sep 9.
Catecholamines are important regulators of homeostasis, yet their functions in hematopoiesis are poorly understood. Here we report that immature human CD34+ cells dynamically expressed dopamine and beta2-adrenergic receptors, with higher expression in the primitive CD34+CD38(lo) population. The myeloid cytokines G-CSF and GM-CSF upregulated neuronal receptor expression on immature CD34+ cells. Treatment with neurotransmitters increased the motility, proliferation and colony formation of human progenitor cells, correlating with increased polarity, expression of the metalloproteinase MT1-MMP and activity of the metalloproteinase MMP-2. Treatment with catecholamines enhanced human CD34+ cell engraftment of NOD-SCID mice through Wnt signaling activation and increased cell mobilization and bone marrow Sca-1+c-Kit+Lin- cell numbers. Our results identify new functions for neurotransmitters and myeloid cytokines in the direct regulation of human and mouse progenitor cell migration and development.
儿茶酚胺是体内稳态的重要调节因子，但其在造血过程中的功能却鲜为人知。在此我们报告，未成熟的人类CD34+细胞动态表达多巴胺和β2-肾上腺素能受体，在原始CD34+CD38(lo)群体中表达更高。髓系细胞因子G-CSF和GM-CSF上调未成熟CD34+细胞上的神经元受体表达。用神经递质处理可增加人类祖细胞的运动性、增殖和集落形成，这与极性增加、金属蛋白酶MT1-MMP的表达及金属蛋白酶MMP-2的活性相关。用儿茶酚胺处理可通过激活Wnt信号增强NOD-SCID小鼠的人类CD34+细胞植入，并增加细胞动员及骨髓Sca-1+c-Kit+Lin-细胞数量。我们的结果确定了神经递质和髓系细胞因子在直接调节人类和小鼠祖细胞迁移及发育方面的新功能。
