Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating β2 integrins

Abstract

To kill pathogens, neutrophils must be able to transmigrate into tissues. Xu and colleagues show that the kinase MYLK, by phosphorylating Pyk2, is required for neutrophils to reach sites of infection. Nonmuscle myosin light-chain kinase (MYLK) mediates increased lung vascular endothelial permeability in lipopolysaccharide-induced lung inflammatory injury, the chief cause of the acute respiratory distress syndrome. In a lung injury model, we demonstrate here that MYLK was also essential for neutrophil transmigration, but that this function was mostly independent of myosin II regulatory light chain, the only known substrate of MYLK. Instead, MYLK in neutrophils was required for the recruitment and activation of the tyrosine kinase Pyk2, which mediated full activation of β2 integrins. Our results demonstrate that MYLK-mediated activation of β2 integrins through Pyk2 links β2 integrin signaling to the actin motile machinery of neutrophils.