@article{3950, 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 beta1 and beta3 integrins on platelets. Impaired activation of beta1, beta2 and beta3 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 beta2 integrin cytoplasmic domain and is essential for neutrophil binding and spreading on beta2 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 beta1, beta2 and beta3 integrin classes, and loss of Kindlin-3 function is sufficient to cause a LAD-III-like phenotype in mice.}, author = {Moser, Markus and Bauer, Martina and Schmid, Stephan and Ruppert, Raphael and Schmidt, Sarah and Michael Sixt and Wang, Hao-Ven and Sperandio, Markus and Fässler, Reinhard}, journal = {Nature Medicine}, number = {3}, pages = {300 -- 305}, publisher = {Nature Publishing Group}, title = {{Kindlin-3 is required for β2 integrin-mediated leukocyte adhesion to endothelial cells}}, doi = {10.1038/nm.1921}, volume = {15}, year = {2009}, }