Sialyltransferase ST3Gal-IV controls CXCR2-mediated firm leukocyte arrest during inflammation.
Sialyltransferase ST3Gal-IV controls CXCR2-mediated firm leukocyte arrest during inflammation.
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DOI：
10.1084/jem.20070846
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发表时间：
2008-06-09
影响因子：
15.3
通讯作者：
Sperandio, Markus
中科院分区：
文献类型：
--
作者：
Frommhold, David;Ludwig, Andreas;Bixel, M. Gabriele;Zarbock, Alexander;Babushkina, Inna;Weissinger, Melitta;Cauwenberghs, Sandra;Ellies, Lesley G.;Marth, Jamey D.;Beck-Sickinger, Annette G.;Sixt, Michael;Lange-Sperandio, Baerbel;Zernecke, Alma;Brandt, Ernst;Weber, Christian;Vestweber, Dietmar;Ley, Klaus;Sperandio, Markus
最近的体外研究表明唾液酸化在趋化因子受体与其配体结合中的作用（Bannert，N.，S.克雷格，M. Farzan，D. Sogah，N.V. Santo，H. Choe和J. Sodroski。2001. J. Exp. 194：1661-1673）。这促使我们研究α 2，3唾液酸转移酶（ST 3Gal-IV）缺陷小鼠炎症提睾肌小静脉中趋化因子诱导的白细胞粘附。我们发现，注射CXCR 2配体CXCL 1（角质形成细胞衍生趋化因子）或CXCL 8（白细胞介素8）后，炎症微血管的白细胞粘附显著减少。此外，ST 3Gal-IV −/−中性粒细胞外渗到巯基乙酸盐预处理的腹膜腔中显著减少。体外试验显示，CXCL 8与分离的ST 3Gal-IV −/−中性粒细胞的结合明显受损。此外，在生理流动条件下，CXCL 1介导的ST 3Gal-IV −/−白细胞粘附以及响应CXCL 1的ST 3Gal-IV −/−白细胞的跨内皮迁移显著减少。在人中性粒细胞中，酶促去唾液酸化降低了CXCR 2配体与中性粒细胞表面的结合，并减少了中性粒细胞对这些趋化因子的脱粒反应。此外，α 2，3-连接的唾液酸特异性怀槐凝集素II与来自经神经氨酸酶处理的CXCR 2转染的HEK 293细胞的纯化CXCR 2的结合显著受损。总的来说，我们提供了大量的证据表明，在体内炎症过程中，ST 3Gal-IV的唾液酸化显著有助于CXCR 2介导的白细胞粘附。
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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影响因子：
6.7
作者：
Laudanna, C;Alon, R
通讯作者：
Alon, R
影响因子：
20.3
作者：
Ehlert, JE;Ludwig, A;Brandt, E
通讯作者：
Brandt, E
影响因子：
5.5
作者：
Smith, David F.;Deem, Tracy L.;Ley, Klaus
通讯作者：
Ley, Klaus
DOI：
10.1152/ajpheart.1997.272.1.h114
发表时间：
1997-01-01
影响因子：
4.8
作者：
Rainger, GE;Fisher, AC;Nash, GB
通讯作者：
Nash, GB
影响因子：
15.3
作者：
Smith, ML;Olson, TS;Ley, K
通讯作者：
Ley, K