| Literature DB >> 19889458 |
Andrew J Wiemer1, Mary A Lokuta, Jill C Surfus, Sarah A Wernimont, Anna Huttenlocher.
Abstract
Proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), are increased in many chronic inflammatory disorders, including rheumatoid arthritis, and contribute to recruitment of neutrophils into areas of inflammation. TNF-alpha induces a stop signal that promotes neutrophil firm adhesion and inhibits neutrophil polarization and chemotaxis. Calpain is a calcium-dependent protease that mediates cytoskeletal reorganization during cell migration. Here, we show that calpain inhibition impairs TNF-alpha-induced neutrophil firm adhesion to fibrinogen-coated surfaces and the formation of vinculin-containing focal complexes. Calpain inhibition induces random migration in TNF-alpha-stimulated cells and prevents the generation of reactive oxygen species, but does not alter TNF-alpha-mediated activation of p38 MAPK and ERK MAPK. These findings suggest that the TNF-alpha-induced neutrophil arrest requires the activity of calpain independent of p38 MAPK and ERK signaling seen after TNF-alpha stimulation. Together, our data suggest that therapeutic inhibition of calpain may be beneficial for limiting TNF-alpha-induced inflammatory responses. Copyright 2010 Elsevier Ltd. All rights reserved.Entities:
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Year: 2009 PMID： 19889458 PMCID： PMC2814964 DOI： 10.1016/j.molimm.2009.10.002
Source DB: PubMed Journal: Mol Immunol ISSN： 0161-5890 Impact factor: 4.407