P-selectin glycoprotein ligand-1 mediates L-selectin-independent leukocyte rolling in high endothelial venules of peripheral lymph nodes.
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.
Harakawa
Nari
N
Department of Internal Medicine, Osaka Dental University, Hirakata, Osaka, Japan.
Shigeta
Akiko
A
Wato
Masahiro
M
Merrill-Skoloff
Glenn
G
Furie
Barbara C
BC
Furie
Bruce
B
Okazaki
Toshiro
T
Domae
Naochika
N
Miyasaka
Masayuki
M
Hirata
Takako
T
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
D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin