Dexamethasone targeted directly to macrophages induces macrophage niches that promote erythroid expansion

Mario Falchi, Lilian Varricchio, Fabrizio Martelli, Francesca Masiello, Giulia Federici, Maria Zingariello, Gabriella Girelli, Carolyn Whitsett, Emanuel F Petricoin, Søren Kragh Moestrup, Ann Zeuner, Anna Rita Migliaccio

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Abstract

    Cultures of human CD34(pos) cells stimulated with erythroid growth factors plus dexamethasone, a model for stress erythropoiesis, generate numerous erythroid cells plus a few macrophages (approx. 3%; 3:1 positive and negative for CD169). Interactions occurring between erythroblasts and macrophages in these cultures and the biological effects associated with these interactions were documented by live phase-contrast videomicroscopy. Macrophages expressed high motility interacting with hundreds/thousands of erythroblasts per hour. CD169(pos) macrophages established multiple rapid 'loose' interactions with proerythroblasts leading to formation of transient erythroblastic island-like structures. By contrast, CD169(neg) macrophages established 'tight' interactions with mature erythroblasts and phagocytosed these cells. 'Loose' interactions of CD169(pos) macrophages were associated with proerythroblast cytokinesis (the M phase of the cell cycle) suggesting that these interactions may promote proerythroblast duplication. This hypothesis was tested by experiments that showed that as few as 103 macrophages significantly increased levels of 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide incorporation frequency in S/G2/M and cytokinesis expressed by proerythroblasts over 24 h of culture. These effects were observed also when macrophages were co-cultured with dexamethasone directly conjugated to a macrophage-specific CD163 antibody. In conclusion, in addition to promoting proerythroblast proliferation directly, dexamethasone stimulates expansion of these cells indirectly by stimulating maturation and cytokinesis supporting activity of macrophages.

    OriginalsprogEngelsk
    TidsskriftHaematologica
    Vol/bind100
    Udgave nummer2
    Sider (fra-til)178-187
    Antal sider10
    ISSN0390-6078
    DOI
    StatusUdgivet - feb. 2015

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