Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating beta2 integrins.
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 beta(2) integrins. Our results demonstrate that MYLK-mediated activation of beta(2) integrins through Pyk2 links beta(2) integrin signaling to the actin motile machinery of neutrophils.
Xu
Jingsong
J
Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA. jingsong@uic.edu
Gao
Xiao-Pei
XP
Ramchandran
Ramaswamy
R
Zhao
You-Yang
YY
Vogel
Stephen M
SM
Malik
Asrar B
AB
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism*; D051379:Mice; D009219:Myosin-Light-Chain Kinase / Q000235:genetics*; D009504:Neutrophils / Q000473:pathology*; D011014:Pneumonia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018805:Sepsis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology
D018821:CD18 Antigens; D009219:Myosin-Light-Chain Kinase