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Originally published online as doi:10.1189/jlb.0608371 on December 1, 2008

Published online before print December 1, 2008
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(Journal of Leukocyte Biology. 2009;85:553-562.)
© 2009 by Society for Leukocyte Biology

Anti-inflammatory and immunosuppressive activation of human monocytes by a bioactive dendrimer

Séverine Fruchon*, Mary Poupot*, Ludovic Martinet*, Cédric-Olivier Turrin{dagger}, Jean-Pierre Majoral{dagger}, Jean-Jacques Fournié*, Anne-Marie Caminade{dagger} and Rémy Poupot*,1

* INSERM, U.563, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France; and Université Paul-Sabatier, Toulouse, France; and
{dagger} Laboratoire de Chimie de Coordination, Toulouse, France

1 Correspondence: INSERM 563, CHU Purpan, BP 3028, 31024 Toulouse Cedex, France. E-mail: remy.poupot{at}inserm.fr

ABSTRACT

The monocyte-macrophage (M{Phi}) lineage can undergo different pathways of activation. The classical priming by IFN-{gamma}, then triggering by LPS, conducts M{Phi} 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.

Key Words: alternative monocyte • gene regulation • chemical mediator