Integrin modulation and signaling in leukocyte adhesion and migration

The movement of leukocytes from the blood into peripheral tissues plays a key role in immunity as well as chronic inflammatory and autoimmune diseases. The shear force of blood flow presents special challenges to leukocytes as they establish adhesion on the vascular endothelium and migrate into the...

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Bibliographic Details
Published in:Immunological reviews 2007-08, Vol.218 (1), p.126-134
Main Authors: Rose, David M, Alon, Ronen, Ginsberg, Mark H
Format: Article
Language:English
Subjects:
Animals
Cell Adhesion
Cell Movement - immunology
Cell Polarity
Humans
integrins
Integrins - immunology
Integrins - metabolism
leukocyte migration
Leukocytes - cytology
Leukocytes - immunology
Leukocytes - metabolism
Signal Transduction - immunology
α4β1
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Summary:The movement of leukocytes from the blood into peripheral tissues plays a key role in immunity as well as chronic inflammatory and autoimmune diseases. The shear force of blood flow presents special challenges to leukocytes as they establish adhesion on the vascular endothelium and migrate into the underlying tissues. Integrins are a family of cell adhesion and signaling molecules, whose function can be regulated to meet these challenges. The affinity of integrins for their vascular ligands can be stimulated in subseconds by chemoattractant signaling. This aids in inducing leukocyte adhesion under flow conditions. Further, linkage of these integrins to the actin cytoskeleton also helps to establish adhesion to the endothelium under flow conditions. In the case of α4β1 integrins, this linkage of the integrin to the cytoskeleton is mediated in part by the binding of paxillin to the α4 integrin subunit and the subsequent binding of paxillin to the cytoskeleton molecule talin. The movement of leukocytes along the vascular endothelium and in between endothelial cells requires the temporal and spatial regulation of small guanosine triphosphatases, such as Rac1. We describe mechanisms through which α4β1 integrin signaling regulates appropriate Rac activation to drive leukocyte migration.
ISSN:0105-2896
1600-065X
DOI:10.1111/j.1600-065X.2007.00536.x