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- Title
Kindlin-3 is required for β<sub>2</sub> integrin–mediated leukocyte adhesion to endothelial cells.
- Authors
Moser, Markus; Bauer, Martina; Schmid, Stephan; Ruppert, Raphael; Schmidt, Sarah; Sixt, Michael; Wang, Hao-Ven; Sperandio, Markus; Fässler, Reinhard
- Abstract
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.
- Subjects
BLOOD cells; BLOOD platelets; LEUCOCYTES; NEUTROPHILS; PHENOTYPES; LABORATORY mice
- Publication
Nature Medicine, 2009, Vol 15, Issue 3, p300
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm.1921