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PMID: 18587400 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating beta2 integrins.

Nature immunology ·Vol. 9 ·No. 8 ·2008-08-00 ·Pages 880-6

Xu J, Gao XP, Ramchandran R, Zhao YY, Vogel SM, Malik AB

Abstract

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.

MeSH Terms
Animals CD18 Antigens/metabolism Mice Myosin-Light-Chain Kinase/genetics Neutrophils/pathology Pneumonia/metabolism,pathology,physiopathology Sepsis/genetics,immunology,physiopathology
Chemicals
CD18 Antigens Myosin-Light-Chain Kinase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Xu Jingsong
Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA. [email protected]
Gao Xiao-Pei
Ramchandran Ramaswamy
Zhao You-Yang
Vogel Stephen M
Malik Asrar B
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1628
Email
[email protected]
Published
2008-08-00
Epub
2008-00-29
Pages
880-6
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2553242
Subset
IM
Grants
NHLBI NIH HHS · R01 HL046350 · United States
NHLBI NIH HHS · P01 HL077806-03 · United States
NHLBI NIH HHS · P01 HL077806 · United States
NHLBI NIH HHS · HL77806 · United States
NHLBI NIH HHS · HL46350 · United States
External Links
PubMed source DOI: 10.1038/ni.1628 PMC Full Text View journal details
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