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Kindlin-3 is required for beta2 integrin-mediated leukocyte adhesion to endothelial cells.
- Source :
-
Nature medicine [Nat Med] 2009 Mar; Vol. 15 (3), pp. 300-5. Date of Electronic Publication: 2009 Feb 22. - Publication Year :
- 2009
-
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.
Details
- Language :
- English
- ISSN :
- 1546-170X
- Volume :
- 15
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nature medicine
- Publication Type :
- Academic Journal
- Accession number :
- 19234461
- Full Text :
- https://doi.org/10.1038/nm.1921