Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling

Autor: Menachem Rubinstein, Neta Netzer, Arnon Nagler, Herzel Ben-Hur, Alexander Kalinkovich, Shoham Shivtiel, Tsvee Lapidot, Asaf Spiegel, Aya Ludin, Igor B. Resnick, Yaara Azaria, Polina Goichberg, Izhar Hardan
Rok vydání: 2007
Předmět:
Zdroj: Nature Immunology. 8:1123-1131
ISSN: 1529-2916
1529-2908
Popis: 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.
Databáze: OpenAIRE