Cooperation of kindlin-3 and talin-1 in integrin activation during neutrophil arrest and inflammation

Neutrophil arrest requires the activation of beta2 integrins. Two FERM
domain proteins, kindlin-3 and talin-1, are necessary for neutrophil
arrest. In this project, we explored the molecular mechanisms of talin-1
and kindlin-3 cooperation during neutrophil adhesion. Flow chamber
experiments showed that talin-1 and kindlin-3 are simultaneously recruited
to the plasma membrane of HL-60 cells during the transition from rolling
to arrest. Using primary neutrophils expressing fluorescent fusion
proteins of talin-1 or kindlin-3, we confirmed that both proteins are
recruited to the plasma membrane at the time of arrest, supporting their
coordinated role in neutrophil integrin activation. In a mouse cremaster
muscle ischemia-reperfusion model, beta2 integrin activation was detected
in neutrophils attached to the endothelium after ischemia-reperfusion.
These findings support that kindlin-3 and talin-1 work together to induce
high-affinity integrin activation during inflammation.