Alpha 2,3-sialyltransferase-IV is essential for L-selectin ligand function in inflammation.
L-selectin belongs to the C-type lectin family of glycoproteins and is constitutively expressed on most leukocytes. L-selectin mediates leukocyte rolling in inflamed microvessels and high endothelial venules (HEV) via binding to specific carbohydrate structures on selectin ligands. Previous studies using sialidase treatment suggested a role of sialic acid residues in L-selectin-dependent rolling. To investigate the role of the alpha2,3-sialyltransferase (ST3Gal)-IV on L-selectin ligand activity in vivo, we studied leukocyte rolling in inflamed venules of the cremaster muscle and in Peyer's patch HEV of ST3Gal-IV-deficient mice and littermate control mice. In cremaster muscle venules with or without TNF-alpha treatment, L-selectin-dependent rolling was almost completely abolished in ST3Gal-IV(-/-) mice. In both models, L-selectin interacts with P-selectin glycoprotein ligand-1 (PSGL-1) presented by adherent leukocytes and leukocyte fragments, but not with endothelial L-selectin ligands. In contrast, L-selectin-dependent rolling in Peyer's patch HEV, which is mediated by unknown endothelial L-selectin ligands, was not impaired in the absence of ST3Gal-IV. Our in vivo data show that PSGL-1, the molecule responsible for L-selectin-mediated leukocyte interactions in inflammation, is dependent on ST3Gal-IV, while alpha2,3-sialylation by ST3Gal-IV is not necessary for L-selectin ligand activity on high endothelial cells of Peyer's patch HEV.
Sperandio
Markus
M
Children's Hospital, University of Heidelberg, Heidelberg, Germany. markus.sperandio@med.uni-heidelberg.de
Frommhold
David
D
Babushkina
Inna
I
Ellies
Lesley G
LG
Olson
Timothy S
TS
Smith
Michael L
ML
Fritzsching
Benedikt
B
Pauly
Eva
E
Smith
David F
DF
Nobiling
Rainer
R
Linderkamp
Otwin
O
Marth
Jamey D
JD
Ley
Klaus
K
D000818:Animals; D002478:Cells, Cultured; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000502:physiology*; D019041:L-Selectin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007962:Leukocytes / Q000473:pathology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019707:Receptors, Chemokine / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012799:Sialyltransferases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
C503133:Gr-1 protein, mouse; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D008024:Ligands; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins; D019041:L-Selectin; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase