The monocyte-macrophage (MΦ) lineage can undergo different pathways of activation. The classical priming by IFN-γ, then triggering by LPS, conducts MΦ toward proinflammatory responses, whereas the alternative activation by IL-4, IL-10, IL-13, or glucocorticoids directs them toward an anti-inflammatory, immunosuppressive phenotype. Recently, we have shown that synthetic phosphorus-containing dendrimers activate human monocytes. Here, we analyzed the gene expression of monocytes activated by an acid azabisphosphonic-capped, phosphorus-containing dendrimer by comparison with untreated monocytes. We found that 78 genes were up-regulated, whereas 62 genes were down-regulated. Analysis of these genes directed the hypothesis of an alternative-like, anti-inflammatory activation of human monocytes. This was confirmed by quantitative RT-PCR and analysis of the surface expression of specific markers by flow cytometry. Functional experiments of inhibition of CD4 + T-lymphocyte proliferation in MLR indicated that dendrimer-activated monocytes ( da -monocytes) have an immune-suppressive phenotype similar to the one induced by IL-4. Moreover, da -monocytes preferentially enhanced amplification of CD4 + T cells, producing IL-10, an immunosuppressive cytokine. Therefore, phosphorus-containing dendrimers appear as new nanobiotools promoting an anti-inflammatory and immunosuppressive activation of human monocytes and thus, prove to be good candidates for innovative, anti-inflammatory immunotherapies.
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Anti-inflammatory and immunosuppressive activation of human monocytes by a bioactive dendrimer
Fruchon, Séverine; Poupot, Mary; Martinet, Ludovic; Turrin, Cédric-Olivier; Majoral, Jean-Pierre; Fournié, Jean-Jacques; Caminade, Anne-Marie; Poupot, Rémy
Follow Journal of Leukocyte Biology
, Volume 85 (3): 553
Fed of American Socs for Experimental Biology – Mar 1, 2009
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