TY - JOUR
T1 - Sialyltransferase ST3Gal-IV controls CXCR2-mediated firm leukocyte arrest during inflammation
AU - Frommhold, David
AU - Ludwig, Andreas
AU - Bixel, M. Gabriele
AU - Zarbock, Alexander
AU - Babushkina, Inna
AU - Weissinger, Melitta
AU - Cauwenberghs, Sandra
AU - Ellies, Lesley G.
AU - Marth, Jamey D.
AU - Beck-Sickinger, Annette G.
AU - Sixt, Michael
AU - Lange-Sperandio, Bärbel
AU - Zernecke, Alma
AU - Brandt, Ernst
AU - Weber, Christian
AU - Vestweber, Dietmar
AU - Ley, Klaus
AU - Sperandio, Markus
PY - 2008/6/9
Y1 - 2008/6/9
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20070846
DO - 10.1084/jem.20070846
M3 - Article
C2 - 18519646
AN - SCOPUS:45149117635
SN - 0022-1007
VL - 205
SP - 1435
EP - 1446
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 6
ER -