International Immunology Advance Access originally published online on January 30, 2007
International Immunology 2007 19(3):321-329; doi:10.1093/intimm/dxl149
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P-selectin glycoprotein ligand-1 mediates L-selectin-independent leukocyte rolling in high endothelial venules of peripheral lymph nodes
1 Department of Internal Medicine, Osaka Dental University, Hirakata, Osaka, Japan
2 Division of Clinical Laboratory Medicine/Hematology, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan
3 The 21st Century Center of Excellence Program, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan
4 Department of Oral Pathology, Osaka Dental University, Hirakata, Osaka, Japan
5 Center for Hemostasis and Thrombosis Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
6 Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Correspondence to: T. Hirata; E-mail: thirata{at}biken.osaka-u.ac.jp
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-1P-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.
Keywords: adhesion molecules, cell trafficking, inflammation, intravital microscopy, lymphocytes
Transmitting editor: H. Karasuyama
Received 27 September 2006, accepted 22 December 2006.
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