A ROLE FOR THE EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF P-SELECTIN IN LIGAND RECOGNITION AND CELL-ADHESION

The selectin family of adhesion molecules mediates the initial interac tions of leukocytes with endothelium. The extracellular region of each selectin contains an amino-terminal C-type lectin domain, followed by an EGF-like domain and multiple short consensus repeat units (SCR). P revious studies have indirectly suggested a role for each of the extra cellular domains of the selectins in cell adhesion. In this study, a p anel of chimeric selectins created by exchange of domains between L- a nd P-selectin was used to directly examine the role of the extracellul ar domains in cell adhesion. Exchange of only the lectin domains betwe en L- and P-selectin conferred the adhesive and ligand recognition fun ctions of the lectin domain of the parent molecule. However, chimeric selectins which contained both the lectin domain of L-selectin and the EGF-like domain of P-selectin exhibited dual ligand-binding specifici ty. These chimeric proteins supported adhesion both to myeloid cells a nd to high endothelial venules (HEV) of lymph nodes and mesenteric ven ules in vivo. Exchange of the SCR domains had no detectable effect on receptor function or specificity. Thus, the EGF-like domain of P-selec tin may play a direct role in ligand recognition and leukocyte adhesio n mediated by P-selectin, with the lectin plus EGF-like domains collec tively forming a functional ligand recognition unit.