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

Research output: Contribution to journalArticlepeer-review

Abstract

Cultures of human CD34pos 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. CD169pos macrophages established multiple rapid ‘loose’ interactions with proerythroblasts leading to formation of transient erythroblas-tic island-like structures. By contrast, CD169neg macrophages established ‘tight’ interactions with mature erythrob-lasts and phagocytosed these cells. ‘Loose’ interactions of CD169pos macrophages were associated with proery-throblast cytokinesis (the M phase of the cell cycle) suggesting that these interactions may promote proerythrob-last 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.

Original languageEnglish
Pages (from-to)178-187
Number of pages10
JournalHaematologica
Volume100
Issue number2
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Hematology

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