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Migration of immature mouse DC across resting endothelium is mediated by ICAM-2 but independent of beta2-integrins and murine DC-SIGN homologues

Item Type:Article
Title:Migration of immature mouse DC across resting endothelium is mediated by ICAM-2 but independent of beta2-integrins and murine DC-SIGN homologues
Creators Name:Wethmar, K. and Helmus, Y. and Luehn, K. and Jones, C. and Laskowska, A. and Varga, G. and Grabbe, S. and Lyck, R. and Engelhardt, B. and Bixel, M.G. and Butz, S. and Loser, K. and Beissert, S. and Ipe, U. and Vestweber, D. and Wild, M.K.
Abstract:Immature dendritic cells (DC) reside in tissues where they initiate immune responses by taking up foreign antigens. Since DC have a limited tissue half-life, the DC pool in tissues has to be replenished constantly. This implies that precursor/immature DC must be able to cross non-activated endothelium using as yet unknown mechanisms. Here we show that immature, but not mature bone marrow-derived murine DC migrate across resting endothelial monolayers in vitro. We find that endothelial intercellular adhesion molecule-2 (ICAM-2) is a major player in transendothelial migration (TEM) of immature DC, accounting for at least 41% of TEM. Surprisingly, the ICAM-2-mediated TEM was independent of beta2-integrins, the known ICAM-2 ligands, since neither blocking of beta2-integrins with antibodies nor the use of CD18-deficient DC affected the ICAM-2-specific TEM. In humans, the C-type lectin DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) was shown to interact with ICAM-2, suggesting a similar role in mice. However, we find that none of the murine DC-SIGN homologues mDC-SIGN, murine DC-SIGN-related molecule-1 (mSIGN-R1) and mSIGN-R3 is expressed on the surface of bone marrow-derived mouse DC. Taken together, this study shows that ICAM-2 strongly supports transmigration of immature DC across resting endothelium by interacting with ligands that are distinct from beta2-integrins and DC-SIGN homologues.
Keywords:CD18, DC-SIGN, Dendritic cells, ICAM-2, Transmigration, Animals, Mice
Source:European Journal of Immunology
ISSN:0014-2980
Publisher:Wiley
Volume:36
Number:10
Page Range:2781-2794
Date:October 2006
Official Publication:https://doi.org/10.1002/eji.200526311
PubMed:View item in PubMed

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