Context-Dependent Role of Vinculin in Neutrophil Adhesion, Motility and Trafficking.

Zachary S Wilson, Hadley Witt, Lauren Hazlett, Michael Harman, Brittany M Neumann, Andrew Whitman, Mohak Patel, Robert S Ross, Christian Franck, Jonathan S Reichner, Craig T Lefort

Scientific reports 2020 Feb 07

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Neutrophils are innate immune effector cells that traffic from the circulation to extravascular sites of inflammation. β2 integrins are important mediators of the processes involved in neutrophil recruitment. Although neutrophils express the cytoskeletal protein vinculin, they do not form mature focal adhesions. Here, we characterize the role of vinculin in β2 integrin-dependent neutrophil adhesion, migration, mechanosensing, and recruitment. We observe that knockout of vinculin attenuates, but does not completely abrogate, neutrophil adhesion, spreading, and crawling under static conditions. However, we also found that vinculin deficiency does not affect these behaviors in the presence of forces from fluid flow. In addition, we identify a role for vinculin in mechanosensing, as vinculin-deficient neutrophils exhibit attenuated spreading on stiff, but not soft, substrates. Consistent with these findings, we observe that in vivo neutrophil recruitment into the inflamed peritoneum of mice remains intact in the absence of vinculin. Together, these data suggest that while vinculin regulates some aspects of neutrophil adhesion and spreading, it may be dispensable for β2 integrin-dependent neutrophil recruitment in vivo.

Citation

Zachary S Wilson, Hadley Witt, Lauren Hazlett, Michael Harman, Brittany M Neumann, Andrew Whitman, Mohak Patel, Robert S Ross, Christian Franck, Jonathan S Reichner, Craig T Lefort. Context-Dependent Role of Vinculin in Neutrophil Adhesion, Motility and Trafficking. Scientific reports. 2020 Feb 07;10(1):2142