Objective: 

Coronin1A (CORO1A), a member of a highly conserved actin binding protein family which is exclusively expressed in leukocytes, regulates reorganization of the cortical actin cytoskeleton. During inflammation, adhesion molecules of the b₂ integrin family (CD11/CD18) are critically involved in the recruitment of polymorphonuclear neutrophils (PMN) to sites of lesion by mediating firm adhesion, spreading and intraluminal crawling. This study was performed to investigate the impact of CORO1A on b₂ integrin-dependent PMN functions.

Methods: 

Murine PMN were isolated from the bone marrow of CORO1A^-/- or wild type mice. Adhesion, spreading and migration on immobilized fibrinogen or ICAM-1 was studied upon stimulation with TNFa, KC or fMLP under static and under flow conditions by time-lapse video microscopy.

Results: 

The genetic absence of CORO1A had no effect on PMN adhesion under static conditions but severely compromised adhesion-dependent functions including spreading and chemotactic migration. Under physiological shear stress conditions, loss of CORO1A resulted in severe impairment of PMN adhesion, spreading and migration. Confocal fluorescence microscopy revealed that CORO1A was highly enriched at the lamellipodium of polarized wild type PMN, whereas CORO1A^-/- PMN were unable to polarize upon induction of adhesion suggesting defective post-adhesion events. Accordingly, we monitored enhanced detachment of CORO1A^-/- PMN under flow conditions indicating that CORO1A function is indispensable for adhesion strengthening.

Conclusion: 

In summary, our data provide evidence for a fundamental role of CORO1A in b₂ integrin-mediated post-arrest functions that are critical for the recruitment of PMN to sites of inflammation namely adhesion strengthening, spreading and crawling.