Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 85, Issue 3, Pages 553-562Publisher
WILEY
DOI: 10.1189/jlb.0608371
Keywords
alternative monocyte; gene regulation; chemical mediator
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Funding
- Institut National de la Sante Et de la Recherche Medicale (INSERM)
- Paul Sabatier University
- Institut National du Cancer [PL 06-87]
- la Ligue Nationale Contre le Cancer
- la Region Midi-Pyrenees
- Rhodia Ltd
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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. J. Leukoc. Biol. 85: 553-562; 2009.
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