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 selectins 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-selectin requires a ligand distinct from the one that supports neutrophil rolling. Tethering under shear to E-selectin requires a carbohydrate ligand that is closely associated with the lectin domain of L-selectin on the neutrophil surface, as enzymatic removal of L-selectin, chemotactic factor-induced shedding of L-selectin, and L-selectin MAbs effectively block tethering. In contrast, this ligand is dispensable for the ability to roll on E-selectin, since rolling adhesions formed after static incubations were not affected by the presence or absence of L-selectin. Thus, E-selectin interactions with ligands on neutrophils persist after L-selectin shedding. These findings add an additional step for regulation of leukocyte localization in inflammatory sites.
Lawrence
M B
MB
Center for Blood Research, Incorporated, Harvard Medical School, Boston, Massachusetts.
Bainton
D F
DF
Springer
T A
TA
D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D048429:Cell Size; D019040:E-Selectin; D006801:Humans; D066298:In Vitro Techniques; D019041:L-Selectin; D008024:Ligands; D016253:Microscopy, Immunoelectron; D009504:Neutrophils / Q000276:immunology / Q000502:physiology* / Q000648:ultrastructure; D012794:Sialic Acids / Q000502:physiology
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D008024:Ligands; D012794:Sialic Acids; D019041:L-Selectin