title: Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling.
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 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.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Asaf
authors.initials: A
authors.lastname: Spiegel
authors.forename: Shoham
authors.initials: S
authors.lastname: Shivtiel
authors.forename: Alexander
authors.initials: A
authors.lastname: Kalinkovich
authors.forename: Aya
authors.initials: A
authors.lastname: Ludin
authors.forename: Neta
authors.initials: N
authors.lastname: Netzer
authors.forename: Polina
authors.initials: P
authors.lastname: Goichberg
authors.forename: Yaara
authors.initials: Y
authors.lastname: Azaria
authors.forename: Igor
authors.initials: I
authors.lastname: Resnick
authors.forename: Izhar
authors.initials: I
authors.lastname: Hardan
authors.forename: Herzel
authors.initials: H
authors.lastname: Ben-Hur
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Menachem
authors.initials: M
authors.lastname: Rubinstein
authors.forename: Tsvee
authors.initials: T
authors.lastname: Lapidot
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis*; D002395:Catecholamines / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology*