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

Journal article

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.

Authors: Wethmar, K; Helmus, Y; Lühn, K; Jones, C; Laskowska, A

• Publication status: Published
• Journal: European journal of immunology
• Volume: 36
• Issue: 10
• Pages: 2781-2794
• Publication date: 2006-10-01
• DOI: 10.1002/eji.200526311
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Flow Cytometry; Antigens, CD18; Antigens, CD; Cloning, Molecular; Mice, Mutant Strains; Dendritic Cells; Animals; Blotting, Western; Cell Differentiation; Immunoprecipitation; Receptors, Cell Surface; Cell Movement; Mice; Humans; Lectins, C-Type; Female; Endothelium, Vascular; Cell Adhesion Molecules; Polymerase Chain Reaction