To identify cell adhesion molecules required for angiogenesis, we used an in vitro model in which bovine capillary endothelial cells can be induced to form capillary-like tubes. Monoclonal antibodies directed against the carbohydrate epitopes sialyl Lewis-X and sialyl Lewis-A inhibited capillary formation. We postulated that a member of the selectin family of adhesion molecules may be involved in capillary formation because these proteins bind to sialyl Lewis-X/A-containing ligands. We isolated a 2.8-kilobase complementary DNA from a bovine capillary endothelial cell cDNA library which encodes a polypeptide with 71% identity to human E-selectin. We report here that antibody directed against the bovine E-selectin inhibited capillary formation, suggesting that in addition to its role in leukocyte adhesion to endothelium, a form of E-selectin is involved in capillary morphogenesis.

A cDNA encoding a homologue of human P-selectin has been isolated from a bovine capillary endothelial cDNA library. The 2.7 kb cDNA encodes a 646 amino acid polypeptide with 77% identity to the human P-selectin except that it lacks three of the consensus repeat domains found in human P-selectin. Human P-selectin, expressed in platelets and endothelium, is a Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. To determine if bovine P-selectin exhibits a similar binding activity, its cDNA was expressed in COS cells and the ability of the transfectants to bind HL-60 human myelogenous leukemia cells was examined. The bovine P-selectin bound the myeloid cells in a manner similar to human P-selectin, indicating that the altered domain structure of bovine P-selectin does not affect P-selectin function in this in vitro cell adhesion assay.