GlyCAM-1 supports leukocyte rolling in flow: Evidence for a greater dynamic stability of L-selectin rolling of lymphocytes than of neutrophils

L-selectin plays a major role in leukocyte traffic through lymph node high endothelial venules (HEV). We have investigated the role of GlyCAM-1, a maj or L-selectin ligand produced by HEV, in mediating leukocyte rolling under in vitro flow conditions. Purified GlyCAM-1 was found to support tethering and rolling in physiological shear flow of both human and murine L-selectin expressing leukocytes at an efficiency comparable to the HEV-derived L-sel ectin ligands termed peripheral node addressin (PNAd). Major dynamic differ ences between L-selectin rolling of peripheral blood T lymphocytes and neut rophils expressing similar L-selectin level were observed on GlyCAM-1. Lymp hocytes established slower and more shear resistant rolling than neutrophil s and could roll on GlyCAM-1 at shear stresses lower than the threshold val ues required for L-selectin-mediated neutrophil rolling. Notably, high stab ility of L-selectin rolling of lymphocytes requires intact cellular energy, although initial lymphocyte tethering to L-selectin ligands is energy-inde pendent. By contrast, L-selectin mediated rolling of neutrophils is insensi tive to energy depletion. The distinct dynamic behavior and energy-dependen ce of L-selectin rolling in different leukocytes suggest that L-selectin ad hesiveness in shear flow is regulated in a cell-type specific manner. The g reater stability of L-selectin rolling of lymphocytes on surface-adsorbed G ly/CAM-1 may contribute to their selective recruitment at peripheral lymph nodes.