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

Research output: Contribution to journalArticlepeer-review

298 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)300-305
Number of pages6
JournalNature Medicine
Issue number3
Publication statusPublished - 2009 Mar

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


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