Kindlin-3 is required for β2 integrin-mediated leukocyte adhesion to endothelial cells

Markus Moser, Martina Bauer, Stephan Schmid, Raphael Ruppert, Sarah Schmidt, Michael Sixt, Hao Ven Wang, Markus Sperandio, Reinhard Fässler

研究成果: Article

235 引文 斯高帕斯(Scopus)

摘要

Integrin activation is essential for the function of all blood cells, including platelets and leukocytes. The blood cell-specific FERM domain protein Kindlin-3 is required for the activation of the β1 and β3 integrins on platelets. Impaired activation of β1, β2 and β3 integrins on platelets and leukocytes is the hallmark of a rare autosomal recessive leukocyte adhesion deficiency syndrome in humans called LAD-III, characterized by severe bleeding and impaired adhesion of leukocytes to inflamed endothelia. Here we show that Kindlin-3 also binds the β2 integrin cytoplasmic domain and is essential for neutrophil binding and spreading on β2 integrin-dependent ligands such as intercellular adhesion molecule-1 and the complement C3 activation product iC3b. Moreover, loss of Kindlin-3 expression abolished firm adhesion and arrest of neutrophils on activated endothelial cells in vitro and in vivo, whereas selectin-mediated rolling was unaffected. Thus, Kindlin-3 is essential to activate the β1, β2 and β3 integrin classes, and loss of Kindlin-3 function is sufficient to cause a LAD-III-like phenotype in mice.

原文English
頁(從 - 到)300-305
頁數6
期刊Nature Medicine
15
發行號3
DOIs
出版狀態Published - 2009 三月 1

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

指紋 深入研究「Kindlin-3 is required for β<sub>2</sub> integrin-mediated leukocyte adhesion to endothelial cells」主題。共同形成了獨特的指紋。

  • 引用此

    Moser, M., Bauer, M., Schmid, S., Ruppert, R., Schmidt, S., Sixt, M., Wang, H. V., Sperandio, M., & Fässler, R. (2009). Kindlin-3 is required for β2 integrin-mediated leukocyte adhesion to endothelial cells. Nature Medicine, 15(3), 300-305. https://doi.org/10.1038/nm.1921