title: P-selectin glycoprotein ligand-1 mediates L-selectin-independent leukocyte rolling in high endothelial venules of peripheral lymph nodes.
abstract: Lymphocyte homing to peripheral lymph nodes (LNs) requires L-selectin. Previous studies, however, suggest that there are L-selectin-independent mechanisms of lymphocyte homing. P-selectin glycoprotein ligand-1 (PSGL-1) is a major ligand for P-selectin expressed in a selectin-binding form on myeloid cells and subsets of lymphoid cells. To discover whether PSGL-1 plays a role in lymphocyte homing, we examined leukocyte rolling and adhesion in the high endothelial venules (HEVs) of the subiliac LNs of wild-type and PSGL-1-deficient mice by intravital microscopy. There were no significant differences in blood velocity or wall shear stress between wild-type and PSGL-1-deficient mice. Although the leukocyte rolling fraction was not altered in PSGL-1-deficient mice, infusion of an anti-L-selectin mAb into these mice completely abolished leukocyte rolling, while the same treatment in wild-type mice inhibited 90% of the leukocyte rolling. This residual rolling in wild-type mice appears to depend on the PSGL-1-P-selectin interaction, since infusion of an anti-L-selectin mAb together with an anti-PSGL-1 mAb or anti-P-selectin mAb almost completely abolished the rolling. PSGL-1 deficiency also led to a higher rolling velocity, suggesting that PSGL-1 mediates leukocyte rolling at low velocities. P-selectin was found to be expressed on the HEVs of subiliac LNs under the conditions of intravital microscopy. Taken together, these results indicate that the interaction of PSGL-1 with P-selectin constitutes a second mechanism of leukocyte rolling in the HEVs of peripheral LNs.
authors.affiliation: Department of Internal Medicine, Osaka Dental University, Hirakata, Osaka, Japan.
authors.forename: Nari
authors.initials: N
authors.lastname: Harakawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Shigeta
authors.forename: Masahiro
authors.initials: M
authors.lastname: Wato
authors.forename: Glenn
authors.initials: G
authors.lastname: Merrill-Skoloff
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Furie
authors.forename: Bruce
authors.initials: B
authors.lastname: Furie
authors.forename: Toshiro
authors.initials: T
authors.lastname: Okazaki
authors.forename: Naochika
authors.initials: N
authors.lastname: Domae
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyasaka
authors.forename: Takako
authors.initials: T
authors.lastname: Hirata
mesh_terms: D000818:Animals; D004729:Endothelium, Lymphatic / Q000276:immunology / Q000378:metabolism*; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism*; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism*; D042601:Lymphatic Vessels / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018715:Microscopy, Video; D019007:P-Selectin / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin