Migration of immature mouse DC across resting enhelium is mediated by ICAM-2 but independent of [bgr] sub(2)-integrins and murine DC-SIGN homologues

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 enhelium using as yet unknown mechanisms. Here we show that immature, but not mature bone marrow- derived murine DC migrate across resting enhelial monolayers in vitro. We find that enhelial intercellular adhesion molecule-2 (ICAM-2) is a major player in transenhelial migration (TEM) of immature DC, accounting for at least 41% of TEM. Surprisingly, the ICAM-2-mediated TEM was independent of [bgr] sub(2)- integrins, the known ICAM-2 ligands, since neither blocking of [bgr] sub(2)- 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 enhelium by interacting with ligands that are distinct from [bgr] sub(2)-integrins and DC-SIGN homologues.