The CD34 family: Sialomucin ligands for 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. 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. CD34 is a transmembrane sialomucin, and a major HEV-ligand for L-selectin. An effort to identify additional ligands has revealed a family of molecules, called the "CD34 Family", which includes the structurally related glycoproteins, CD34, podocalyxin, and endoglycan. All three molecules share a similar overall domain organization, consisting of an extracellular mucin domain, followed by a cysteine-containing and presumably globular domain, a transmembrane region, and a sizeable cytoplasmic tail. In addition, endoglycan possesses an amino-terminal highly acidic domain and is modified with chondroitin sulfate. All of these molecules are expressed broadly by endothelium including HEV. When properly modified (as in HEV) all three family members can mediate the L-selectin-dependent adhesion of lymphocytes under flow conditions.; At least two HEV-ligands for L-selectin still remain unidentified. In an effort to characterize these glycoproteins, L-selectin-reactive components were identified in human serum. Peptide microsequencing of this material revealed the presence of a soluble form of CD34 as well as a novel sialomucin(s). A continuation of this effort should lead to the definition of the complete set of HEV-ligands for L-selectin.; The firm adhesion and transmigration of lymphocytes across HEV is critically dependent on chemokines, which are immobilized on the endothelial surface. The acidic amino-terminal domain of endoglycan was found to specifically bind a subset of chemokines which act at the endothelial surface. Thus, endoglycan's ability bind chemokines, along with its localization on the lumen of HEV make it an attractive candidate as a "presentation molecule" for chemokines that act on blood-borne leukocytes. In addition to their endothelial expression, members of the CD34 family are also found on multipotent hematopoietic progenitors. This not only provides multiple markers for the isolation or quantitation of these clinically important cells, but also suggests a functional role for these molecules in hematopoiesis.