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Nat Immunol ; 8(10): 1123-31, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17828268

RESUMO

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.


Assuntos
Antígenos CD34/análise , Catecolaminas/farmacologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Neurotransmissores/farmacologia , Transdução de Sinais/fisiologia , Proteínas Wnt/fisiologia , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dopamina/farmacologia , Agonistas de Dopamina/farmacologia , Células-Tronco Hematopoéticas/citologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Norepinefrina/farmacologia , Receptores Dopaminérgicos/análise
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