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          Institute: MPI für molekulare Biomedizin     Collection: Yearbook 2013     Display Documents



  history
ID: 648321.0, MPI für molekulare Biomedizin / Yearbook 2013
Severe impairment of leukocyte recruitment in ppGalNAcT-1-deficient mice
Authors:Block, H.; Ley, K.; Zarbock, A.
Date of Publication (YYYY-MM-DD):2012-06-01
Title of Journal:J Immunol
Volume:188
Issue / Number:11
Start Page:5674
End Page:5681
Review Status:Internal review
Audience:Not Specified
Abstract / Description: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-alpha-treated cremaster muscles comparing ppGalNAcT-1-deficient mice (Galnt1(-/-)) and wild-type mice. In untreated and TNF-alpha-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.
Free Keywords:Animals; Carbohydrate Conformation; Cell Movement/genetics/*immunology; Inflammation/enzymology/genetics/immunology; Leukocyte Rolling/genetics/*immunology; Ligands; Membrane Glycoproteins/metabolism; Mice; Mice, Knockout; N-Acetylgalactosaminyltransferases/*deficiency/genetics/metabolism; P-Selectin/metabolism; Polysaccharides/metabolism; Radiation Chimera; Severity of Illness Index
External Publication Status:published
Document Type:Article
Communicated by:keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:%G eng
Identifiers:ISSN:1550-6606 (Electronic) 0022-1767 (Linking) %R 10.4... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/22544932 [ID No:2]
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