An L-selectin ligand distinct from P-selectin glycoprotein ligand-1 is expressed on endothelial cells and promotes neutrophil rolling in inflammation.
Neutrophils recruited from the blood are key players in the innate immune response. Selectins play critical roles in neutrophil recruitment by mediating their tethering and rolling in inflamed venules. While the roles of P- and E-selectin in this process are well established, the mechanisms of L-selectin-mediated neutrophil recruitment remain elusive. One proposal is that tethering is mediated by L-selectin on flowing neutrophils interacting with P-selectin glycoprotein ligand-1 (PSGL-1) on adherent neutrophils. To clarify whether L-selectin-mediated neutrophil recruitment depends entirely on PSGL-1, we examined the impact of L-selectin deficiency in mice with a PSGL-1-deficient background. L-selectin and PSGL-1 double-knockout mice exhibited a higher increase in their peripheral blood neutrophil count and a worse defect in neutrophil recruitment into the inflamed peritoneum than PSGL-1-deficient mice. Intravital microscopy of inflamed cremaster muscle venules showed that L-selectindeficiency or antibody blockade of L-selectin reduced the residual leukocyte rolling in PSGL-1-deficient mice. Flow cytometric analyses showed that the endothelial cells from the cremaster muscle bound L-selectin in a PSGL-1-independent manner. These results provide evidence for the existence of an L-selectin ligand distinct from PSGL-1 in inflammation and indicate that such a ligand is expressed on endothelial cells, promoting neutrophil rolling in vivo.
Shigeta
Akiko
A
Laboratory of Combined Research on Microbiology and Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Matsumoto
Masanori
M
Tedder
Thomas F
TF
Lowe
John B
JB
Miyasaka
Masayuki
M
Hirata
Takako
T
D000818:Animals; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000737:chemistry*; D007249:Inflammation / Q000276:immunology*; D019041:L-Selectin / Q000378:metabolism*; D036904:Leukocyte Rolling / Q000276:immunology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology; D009504:Neutrophils / Q000276:immunology*
D008024:Ligands; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D019041:L-Selectin