Binding of the adhesion and pathogen receptor DC-SIGN by monocytes is regulated by the density of Lewis X molecules.
Soluble DC-SIGN (CD209) bind unsialylated Lewis X epitopes that are abundantly expressed on neutrophils. Due to the low expression of unsialylated Lewis X epitopes on monocytes, no binding of soluble DC-SIGN molecules was seen. In contrast, beads coated with multiple DC-SIGN molecules show a high percentage of binding to monocytes. The increased number of DC-SIGN molecules present on the beads enable multivalent interactions between the DC-SIGN molecules and the scarce Lewis X epitopes present on monocytes. Increased expression of unsialylated Lewis X epitopes on monocytes after neuraminidase treatment coincided with enhanced binding to soluble DC-SIGN. Multiple unsialylated Lewis X epitopes in close proximity of each other are now able to interact multivalently to soluble DC-SIGN. From these findings, we conclude that firm interactions between DC-SIGN and monocytes can be established by either increasing the density of DC-SIGN molecules at the cell surface or by increasing the number of Lewis X epitopes. Regulating the number of ligands endows monocytes with the capacity to modulate binding to DC-SIGN. This may result in a bi-directional cross-talk between DC and monocytes, to modulate innate and/or adaptive immune responses.
Gijzen
Karlijn
K
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Broers
Karin M
KM
Beeren
Inge M J
IM
Figdor
Carl G
CG
Torensma
Ruurd
R
D015815:Cell Adhesion Molecules / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology*; D016256:Lewis X Antigen / Q000276:immunology*; D008863:Microspheres; D009000:Monocytes / Q000276:immunology* / Q000648:ultrastructure; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D016256:Lewis X Antigen; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin