Sialyltransferase ST3Gal-IV controls CXCR2-mediated firm leukocyte arrest during inflammation

David Frommhold, Andreas Ludwig, M. Gabriele Bixel, Alexander Zarbock, Inna Babushkina, Melitta Weissinger, Sandra Cauwenberghs, Lesley G. Ellies, Jamey D. Marth, Annette G. Beck-Sickinger, Michael Sixt, Bärbel Lange-Sperandio, Alma Zernecke, Ernst Brandt, Christian Weber, Dietmar Vestweber, Klaus Ley, Markus Sperandio

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Recent in vitro studies have suggested a role for sialylation in chemokine receptor binding to its ligand (Bannert, N., S. Craig, M. Farzan, D. Sogah, N.V. Santo, H. Choe, and J. Sodroski. 2001. J. Exp. Med. 194:1661-1673). This prompted us to investigate chemokine-induced leukocyte adhesion in inflamed cremaster muscle venules of α2,3 sialyltransferase (ST3Gal-IV)-deficient mice. We found a marked reduction in leukocyte adhesion to inflamed microvessels upon injection of the CXCR2 ligands CXCL1 (keratinocyte-derived chemokine) or CXCL8 (interleukin 8). In addition, extravasation of ST3Gal-IV-/- neutrophils into thioglycollate-pretreated peritoneal cavities was significantly decreased. In vitro assays revealed that CXCL8 binding to isolated ST3Gal-IV-/- neutrophils was markedly impaired. Furthermore, CXCL1-mediated adhesion of ST3Gal-IV-/- leukocytes at physiological flow conditions, as well as transendothelial migration of ST3Gal-IV -/- leukocytes in response to CXCL1, was significantly reduced. In human neutrophils, enzymatic desialylation decreased binding of CXCR2 ligands to the neutrophil surface and diminished neutrophil degranulation in response to these chemokines. In addition, binding of α2,3-linked sialic acid-specific Maackia amurensis lectin II to purified CXCR2 from neuraminidase-treated CXCR2-transfected HEK293 cells was markedly impaired. Collectively, we provide substantial evidence that sialylation by ST3Gal-IV significantly contributes to CXCR2-mediated leukocyte adhesion during inflammation in vivo.

Original languageEnglish (US)
Pages (from-to)1435-1446
Number of pages12
JournalJournal of Experimental Medicine
Issue number6
StatePublished - Jun 9 2008
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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