Article abstract
Nature Immunology 8, 1123 - 1131 (2007)
Published online: 9 September 2007 | doi:10.1038/ni1509
Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling
Asaf Spiegel1, Shoham Shivtiel1, Alexander Kalinkovich1, Aya Ludin1, Neta Netzer1, Polina Goichberg1, Yaara Azaria1, Igor Resnick2, Izhar Hardan3, Herzel Ben-Hur4, Arnon Nagler3, Menachem Rubinstein5 & Tsvee Lapidot1
Abstract
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 
2-adrenergic receptors, with higher expression in the primitive CD34+CD38lo 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.
- Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
- Department of Bone Marrow Transplantation & Cancer Immunotherapy, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
- Department of Hematology & Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel.
- Assaf Haroffe Medical Center, Tsrifin 70300, Israel.
- Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
Correspondence to: Tsvee Lapidot1 e-mail: tsvee.lapidot@weizmann.ac.il
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