Migration of immature mouse DC across resting endothelium is mediated by ICAM-2 but independent of beta2-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 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.
Wethmar
Klaus
K
Max Planck Institute for Molecular Biomedicine, Münster, Germany, and Institute of Cell Biology, ZMBE, University of Münster, Münster, Germany.
Helmus
Yvonne
Y
Lühn
Kerstin
K
Jones
Claire
C
Laskowska
Anna
A
Varga
Georg
G
Grabbe
Stephan
S
Lyck
Ruth
R
Engelhardt
Britta
B
Bixel
M Gabriele
MG
Butz
Stefan
S
Loser
Karin
K
Beissert
Stefan
S
Ipe
Ute
U
Vestweber
Dietmar
D
Wild
Martin K
MK
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015153:Blotting, Western; D018821:CD18 Antigens / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D003001:Cloning, Molecular; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D037181:Lectins, C-Type / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C480027:ICAM-2 protein, mouse