Molecular cloning of a dendritic cell-associated transmembrane protein, DC-HIL, that promotes RGD-dependent adhesion of endothelial cells through recognition of heparan sulfate proteoglycans

We isolated a novel molecule (DC-HIL) expressed abundantly by the XS52 dend ritic cell (DC) line and epidermal Langerhans cells, but minimally by other cell lines. DC-HIL is a type I transmembrane protein that contains a hepar in-binding motif and an integrin-recognition motif, RGD, in its extracellul ar domain (ECD), A soluble fusion protein (DC-HIL-Fc) of the ECD and an imm unoglobulin Fc bound to the surface of an endothelial cell line (SVEC). Thi s binding induced adhesion of SVEC to its immobilized form. Sulfated polysa ccharides (e.g. heparin and fucoidan) inhibited binding of soluble DC-HIL-F c and adhesion of SVEC. By contrast, an integrin inhibitor (RGDS tetramer) had no effect on binding to SVEC, but prevented adhesion of SVEC, This diff erential RGD requirement was confirmed by the finding that DC-HIL-Fc mutant lacking the RGD motif can bind to SVEC but is unable to induce adhesion of SVEC. Furthermore, DC-HIL appears to recognize directly these sulfated pol ysaccharides. These results suggest that DC-HIL binds to SVEC by recognizin g heparan sulfate proteoglycans on endothelial cells, thereby inducing adhe sion of SVEC in an RGD-dependent manner. We propose that DC-HIL serves as a DC-associated, heparan sulfate proteoglycan-dependent integrin ligand, whi ch may be involved in transendothelial migration of DC.