NEUTROPHIL TETHERING TO AND ROLLING ON E-SELECTIN ARE SEPARABLE BY REQUIREMENT FOR L-SELECTIN

Neutrophil tethering and rolling in shear flow are mediated by selecti ns and have been thought to be two indistinguishable manifestations of a single molecular interaction between selectin and ligand. However, we report that under physiologic flow conditions, tethering to E-selec tin requires a ligand distinct from the one that supports neutrophil r olling. Tethering under shear to E-selectin requires a carbohydrate li gand that is closely associated with the lectin domain of L-selectin o n the neutrophil surface, as enzymatic removal of L-selectin, chemotac tic factor-induced shedding of L-selectin, and L-selectin MAbs effecti vely block tethering. In contrast, this ligand is dispensable for the ability to roll on E-selectin, since rolling adhesions formed after st atic incubations were not affected by the presence or absence of L-sel ectin. Thus, E-selectin interactions with ligands on neutrophils persi st after L-selectin shedding. These findings add an additional step fo r regulation of leukocyte localization in inflammatory sites.