title: Severe impairment of leukocyte recruitment in ppGalNAcT-1-deficient mice.
abstract: P-selectin glycoprotein ligand-1 plays an important role in leukocyte recruitment. Its binding affinity to selectins is modulated by posttranslational modifications. The polypeptide N-acetylgalactosamine transferase-1 (ppGalNAcT-1) initiates core-type protein O-glycosylation. To address whether the glycosylation of P-selectin glycoprotein ligand-1 by ppGalNAcT-1 is important for leukocyte recruitment in vivo, we investigated leukocyte recruitment in untreated and TNF-α-treated cremaster muscles comparing ppGalNAcT-1-deficient mice (Galnt1(-/-)) and wild-type mice. In untreated and TNF-α-treated Galnt1(-/-) mice, leukocyte rolling, adhesion, and transmigration were significantly reduced, with markedly increased rolling velocity compared with control mice. L-selectin-dependent leukocyte rolling was completely abolished in Galnt1(-/-) mice compared with wild-type mice. Thioglycollate-induced peritonitis experiments with chimeric mice revealed that hematopoietic ppGalNAcT-1 is important for leukocyte recruitment. These data show that the loss of ppGalNAcT-1 led to reduced leukocyte rolling and recruitment and increased rolling velocity, suggesting a predominant role for ppGalNAcT-1 in attaching functionally relevant O-linked glycans to selectin ligands.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of Münster, 48151 Münster, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Block
authors.forename: Klaus
authors.initials: K
authors.lastname: Ley
authors.forename: Alexander
authors.initials: A
authors.lastname: Zarbock
mesh_terms: D000818:Animals; D002236:Carbohydrate Conformation; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D036904:Leukocyte Rolling / Q000235:genetics / Q000276:immunology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017350:N-Acetylgalactosaminyltransferases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism; D011828:Radiation Chimera; D012720:Severity of Illness Index; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D008024:Ligands; D008562:Membrane Glycoproteins; D017350:N-Acetylgalactosaminyltransferases; D019007:P-Selectin; D011134:Polysaccharides; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C084882:P-selectin ligand protein