Published online 31 July 2009
Haematologica, Vol 94, Issue 11, 1502-1512 doi:10.3324/haematol.2009.010934
Copyright © 2009 by Ferrata Storti Foundation
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Phagocytes

Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases

Fanny Angelot1, Estelle Seillès1, Sabeha Biichlé1, Yael Berda2, Béatrice Gaugler1, Joel Plumas3, Laurence Chaperot3, Françoise Dignat-George2, Pierre Tiberghien1, Philippe Saas1, Francine Garnache-Ottou1

1 Inserm UMR645, University of Franche-Comté, EFS Bourgogne Franche-Comté, IFR133, Besançon, France
2 Inserm U608, Laboratoire d’Hématologie et d’Immunologie, UFR de Pharmacie, Université de la Méditerranée, Marseille, France
3 Inserm U823, EFS du sang Rhône Alpes, Université Joseph Fourier, La Tronche, France

Correspondence: Francine Garnache-Ottou, 1 Bd A. Fleming, BP1937, F25020 Besançon cedex, France. E-mail:francine.garnache{at}efs.sante.fr

Background: Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies.

Design and Methods: Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions.

Results: Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-{alpha}) and also induced allogeneic naive CD4+ T cells to proliferate and to produce type 1 cytokines such as interferon-{gamma} and tumor necrosis factor-{alpha}. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation.

Conclusions: Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in various inflammatory disorders and endothelial microparticles could be an important immunmodulatory therapeutic target.

Key words: endothelial cell-derived microparticles, plasmacytoid, inflammatory diseases, dendritic cells.