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Kindlin-3 is required for β2 integrin–mediated leukocyte adhesion to endothelial cells.
- Source :
- Nature Medicine; Mar2009, Vol. 15 Issue 3, p300-305, 6p, 4 Graphs
- 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 β<subscript>1</subscript> and β<subscript>3</subscript> integrins on platelets. Impaired activation of β<subscript>1</subscript>, β<subscript>2</subscript> and β<subscript>3</subscript> 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 β<subscript>2</subscript> integrin cytoplasmic domain and is essential for neutrophil binding and spreading on β<subscript>2</subscript> 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 β<subscript>1</subscript>, β<subscript>2</subscript> and β<subscript>3</subscript> integrin classes, and loss of Kindlin-3 function is sufficient to cause a LAD-III–like phenotype in mice. [ABSTRACT FROM AUTHOR]
- Subjects :
- BLOOD cells
BLOOD platelets
LEUCOCYTES
NEUTROPHILS
PHENOTYPES
LABORATORY mice
Subjects
Details
- Language :
- English
- ISSN :
- 10788956
- Volume :
- 15
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Nature Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 36818266
- Full Text :
- https://doi.org/10.1038/nm.1921