TY - JOUR
T1 - α2,3-sialyltransferase-IV is essential for L-selectin ligand function in inflammation
AU - Sperandio, Markus
AU - Frommhold, David
AU - Babushkina, Inna
AU - Ellies, Lesley G.
AU - Olson, Timothy S.
AU - Smith, Michael L.
AU - Fritzsching, Benedikt
AU - Pauly, Eva
AU - Smith, David F.
AU - Nobiling, Rainer
AU - Linderkamp, Otwin
AU - Marth, Jamey D.
AU - Ley, Klaus
PY - 2006/12
Y1 - 2006/12
N2 - 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 α2,3-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-α 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 ST3GaI-IV, while α2,3-sialylation by ST3Gal-IV is not necessary for L-selectin ligand activity on high endothelial cells of Peyer's patch HEV.
AB - 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 α2,3-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-α 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 ST3GaI-IV, while α2,3-sialylation by ST3Gal-IV is not necessary for L-selectin ligand activity on high endothelial cells of Peyer's patch HEV.
KW - Adhesion
KW - Inflammation
KW - Neutrophils
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U2 - 10.1002/eji.200636157
DO - 10.1002/eji.200636157
M3 - Article
C2 - 17111351
AN - SCOPUS:33845570625
SN - 0014-2980
VL - 36
SP - 3207
EP - 3215
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 12
ER -