The HEV-derived ligands for L-selectin consist of a group of mucin-like glycoproteins which are able to present dense clusters of sulfated and sialylated O-linked oligosaccharides to L-selectin ( 12).
The NH 2-terminal C-type lectin domain of L-selectin mediates adhesion by binding to specific carbohydrate structures presented by glycoprotein ligands on the vascular endothelium ( 11). Studies using antibody blockade as well as gene inactivation have demonstrated the absolute requirement for L-selectin in the recruitment of lymphocytes to peripheral lymph nodes as well as a major role in recruitment into Peyer's patches and certain sites of inflammation ( 7– 10). This lectin-like adhesion molecule is responsible for the initial tethering and rolling of lymphocytes on the endothelium before their integrin-mediated firm arrest and transmigration ( 5, 6). These vessels are defined by the distinct, cuboidal morphology of their endothelial cells ( 3) and their luminal presentation of ligands for the leukocyte adhesion molecule, L-selectin ( 4). Lymphocyte recruitment from the blood into all secondary lymphoid organs (except the spleen) as well as into many sites of chronic inflammation is mediated by specialized postcapillary venules called high endothelial venules (HEV) 1 ( 2). Maintenance of immune surveillance depends on the constant recirculation of lymphocytes from the blood through the vascular wall into the tissues and eventually back into the blood ( 1).
These results suggest a novel function for PCLP as an adhesion molecule and allow the definition of conserved structural features in PCLP and CD34, which may be important for L-selectin ligand function. Furthermore, purified HEV-derived PCLP is able to support the tethering and rolling of lymphocytes under physiological flow conditions in vitro. We have determined that PCLP is present on HEV, where it binds to both recombinant L-selectin and the HEV-specific monoclonal antibody MECA-79. PCLP has been shown previously to be expressed on the foot processes of podocytes in the kidney glomerulus as well as on vascular endothelium at some sites. Podocalyxin-like protein (PCLP) is a transmembrane sialomucin that is similar in structure to the well-characterized L-selectin ligand CD34. Although the HEV-derived ligands for L-selectin are still incompletely defined, they share a common sialomucin-like structure which is thought to present clustered oligosaccharides to the lectin domain of L-selectin. The leukocyte adhesion molecule, L-selectin, mediates the recruitment of lymphocytes to secondary lymphoid organs via interactions with specific ligands presented on high endothelial venules (HEV).