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© Valérie Choumet
Mosquitoes were orally infected with the chikungunya virus. Midguts were dissected at day 5 post-infection, fixed and permeabilised. Virus is shown in red (anti-E2 protein, cyanine 3), the actin network in green (phalloidin 548) and nuclei in blue (DAPI).
Publication : Leukemia

Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Leukemia - 15 Apr 2011

Dar A, Schajnovitz A, Lapid K, Kalinkovich A, Itkin T, Ludin A, Kao WM, Battista M, Tesio M, Kollet O, Cohen NN, Margalit R, Buss EC, Baleux F, Oishi S, Fujii N, Larochelle A, Dunbar CE, Broxmeyer HE, Frenette PS, Lapidot T

Link to Pubmed [PMID] – 21494253

Leukemia 2011 Aug;25(8):1286-96

Steady-state egress of hematopoietic progenitor cells can be rapidly amplified by mobilizing agents such as AMD3100, the mechanism, however, is poorly understood. We report that AMD3100 increased the homeostatic release of the chemokine stromal cell derived factor-1 (SDF-1) to the circulation in mice and non-human primates. Neutralizing antibodies against CXCR4 or SDF-1 inhibited both steady state and AMD3100-induced SDF-1 release and reduced egress of murine progenitor cells over mature leukocytes. Intra-bone injection of biotinylated SDF-1 also enhanced release of this chemokine and murine progenitor cell mobilization. AMD3100 directly induced SDF-1 release from CXCR4(+) human bone marrow osteoblasts and endothelial cells and activated uPA in a CXCR4/JNK-dependent manner. Additionally, ROS inhibition reduced AMD3100-induced SDF-1 release, activation of circulating uPA and mobilization of progenitor cells. Norepinephrine treatment, mimicking acute stress, rapidly increased SDF-1 release and progenitor cell mobilization, whereas β2-adrenergic antagonist inhibited both steady state and AMD3100-induced SDF-1 release and progenitor cell mobilization in mice. In conclusion, this study reveals that SDF-1 release from bone marrow stromal cells to the circulation emerges as a pivotal mechanism essential for steady-state egress and rapid mobilization of hematopoietic progenitor cells, but not mature leukocytes.

http://www.ncbi.nlm.nih.gov/pubmed/21494253