Journal
JOURNAL OF IMMUNOLOGY
Volume 187, Issue 8, Pages 4360-4368Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1003725
Keywords
-
Categories
Funding
- Canadian Institutes of Health Research [MOP-89740]
- Heart and Stroke Foundation of Ontario
Ask authors/readers for more resources
Chemokine/chemoattractant G protein-coupled receptors trigger an inside-out signaling network that rapidly activates integrins, a key step in inflammatory leukocyte recruitment. Integrins mediate leukocyte arrest and adhesion to endothelium through multivalent binding, and they transmit outside-in signals to stabilize adhesion and coordinate cell spreading and migration. In the present study, we used RNA interference in the U937 monocytic cell line to investigate the role of talin-1, kindlin-3, and alpha-actinin-1 in the fMLF- and SDF-1 alpha-induced upregulation of alpha(4)beta(1) integrin affinity and consequent adhesive events. Affinity upregulation of alpha(4)beta(1) integrin was not impaired by small interfering RNA knockdown of talin-1, kindlin-3, or alpha-actinin-1. Only kindlin-3 knockdown increased flow-induced detachment from VCAM-1-coated surfaces in response to fluid flow, whereas knockdown of either talin-1 or kindlin-3 increased detachment from ICAM-1-coated surfaces. Biochemical analyses revealed that alpha(4)beta(1) expression was highly enriched in U937 cell microridges and murine lymphocyte microvilli. Kindlin-3 was present throughout the cell, whereas talin-1 was largely excluded from microridges/microvilli. The subcellular colocalization of alpha(4)beta(1) and kindlin-3 in microridges may explain why kindlin-3 rapidly associates with alpha(4)beta(1) after G protein-coupled receptor signaling and contributes to adhesion strengthening. Talin-1 contributed to alpha(4)beta(1)-dependent chemotaxis, suggesting that it participates in a later stage of the leukocyte adhesion cascade when the leukocyte cytoskeleton undergoes dramatic rearrangement. The Journal of Immunology, 2011, 187: 4360-4368.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available