Calpain inhibition impairs TNF-α-mediated neutrophil adhesion, arrest and oxidative burst

Andrew J. Wiemer, Mary A. Lokuta, Jill C. Surfus, Sarah A. Wernimont, Anna Huttenlocher

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), are increased in many chronic inflammatory disorders, including rheumatoid arthritis, and contribute to recruitment of neutrophils into areas of inflammation. TNF-α 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-α-induced neutrophil firm adhesion to fibrinogen-coated surfaces and the formation of vinculin-containing focal complexes. Calpain inhibition induces random migration in TNF-α-stimulated cells and prevents the generation of reactive oxygen species, but does not alter TNF-α-mediated activation of p38 MAPK and ERK MAPK. These findings suggest that the TNF-α-induced neutrophil arrest requires the activity of calpain independent of p38 MAPK and ERK signaling seen after TNF-α stimulation. Together, our data suggest that therapeutic inhibition of calpain may be beneficial for limiting TNF-α-induced inflammatory responses.

Original languageEnglish (US)
Pages (from-to)894-902
Number of pages9
JournalMolecular Immunology
Issue number4
StatePublished - Jan 2010
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by NIH NIAID R01 to A.H. [ AI068062 ]. Postdoctoral support was provided to A.J.W. by the University of Wisconsin Institute on Aging Training Grant (NIH [ T32AG000213-17 ], Sanjay Asthana, P.I.). We would like to thank Gary Bokoch for useful discussions.


  • Migration
  • Motility
  • Neutrophil
  • Oxidative burst
  • Stop signal
  • Tumor necrosis factor


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