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TNF‐α promotes a stop signal that inhibits neutrophil polarization and migration via a p38 MAPK pathway
Author(s) -
Lokuta Mary A.,
Huttenlocher Anna
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0205067
Subject(s) - tumor necrosis factor alpha , mapk/erk pathway , p38 mitogen activated protein kinases , chemotaxis , biology , proinflammatory cytokine , signal transduction , microbiology and biotechnology , inflammation , immunology , cancer research , receptor , biochemistry
Neutrophils are a major component of the inflammatory response in patients with asthma and other inflammatory conditions. Proinflammatory cytokines, such as tumor necrosis factor α (TNF‐α), are increased in the airway of patients with severe asthma and have been implicated in the recruitment of neutrophils into areas of inflammation. Here, we show that TNF‐α induces a stop signal that promotes firm neutrophil adhesion and inhibits neutrophil polarization and chemotaxis to chemoattractants including interleukin‐8 and C5a. TNF‐α treatment of neutrophils plated on a fibrinogen‐coated surface promotes firm neutrophil adhesion and the formation of vinculin‐containing focal complexes. TNF‐α induces a more than tenfold increase in p38 mitogen‐activated protein kinase (MAPK) but not extracellular signal‐regulated kinase phosphorylation. Inhibition of p38 MAPK in neutrophils treated with TNF‐α causes neutrophil polarization and motility. These findings suggest that TNF‐α initiates a stop signal through a p38 MAPK pathway, which may promote the retention of neutrophils in inflammatory sites. Together, our data suggest that inhibition of p38 MAPK may be an attractive target to limit inflammatory responses that are mediated by TNF‐α.