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Polymorphonuclear Neutrophil-Derived Ectosomes Interfere with the Maturation of Monocyte-Derived Dendritic Cells¹

Ceylan Eken^2,*, Olivier Gasser^*, Gabriela Zenhaeusern, Ineke Oehri, Christoph Hess and Jürg A. Schifferli^*

^* Department of Research, Immunonephrology Laboratory; and Department of Research, Immunobiology Laboratory, University Hospital Basel, Basel, Switzerland

Polymorphonuclear neutrophils (PMNs) are a key component of the innate immune system. Their activation leads to the release of potent antimicrobial agents through degranulation. Simultaneously, PMNs release cell surface-derived microvesicles, so-called ectosomes (PMN-Ect). PMN-Ect are rightside-out vesicles with a diameter of 50–200 nm. They expose phosphatidylserine in the outer leaflet of their membrane and down-modulate monocyte/macrophage-activation in vitro. In this study, we analyzed the effects of PMN-Ect on maturation of human monocyte-derived dendritic cells (MoDCs). Intriguingly, exposing immature MoDCs to PMN-Ect modified their morphology, reduced their phagocytic activity, and increased the release of TGF-β1. When immature MoDCs were incubated with PMN-Ect and stimulated with the TLR4 ligand LPS, the maturation process was partially inhibited as evidenced by reduced expression of cell surface markers (CD40, CD80, CD83, CD86, and HLA-DP DQ DR), inhibition of cytokine-release (IL-8, IL-10, IL-12, and TNF-), and a reduced capacity to induce T cell proliferation. Together these data provide evidence that PMN-Ect have the ability to modify MoDC maturation and function. PMN-Ect may thus represent an as yet unidentified host-factor influencing MoDC maturation at the site of injury, thereby possibly impacting on downstream MoDC-dependent immunity.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Swiss National Science Foundation Grants 32000-116839 and PP00B-114850, the Roche Foundation for Anemia Research, and Fondazione per la Ricerca Sulla Trasfusione e Sui Trapianti.

² Address correspondence and reprint requests to Ceylan Eken, University Hospital Basel, Immunonephrology Laboratory, Hebelstrasse 20, Basel 4031, Switzerland. E-mail address: ceylan.eken{at}unibas.ch

³ Abbreviations used in this paper: Ect, ectosome; PMN, polymorphonuclear neutrophil; PS, phosphatidylserine; DC, dendritic cell; iDC, immature DC; MoDC, monocyte-derived DC; iMoDC, immature MoDC; mMoDC, matured MoDC; MFI, mean fluorescence intensity; AnV, annexin V; FSC, forward scatter; SSC, side scatter.