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Cutting edge: Slamf8 is a negative regulator of Nox2 activity in macrophages.

Slamf8 (CD353) is a cell surface receptor that is expressed upon activation of macrophages (MΦs) by IFN-γ or bacteria. In this article, we report that a very high NADPH oxidase (Nox2) enzyme activity was found in Slamf8(-/-) MΦs in response to Escherichia coli or Staphylococcus aureus, as well as to PMA. The elevated Nox2 activity in Slamf8(-/-) MΦs was also demonstrated in E. coli or S. aureus phagosomes by using a pH indicator system and was further confirmed by a reduction in the enzyme activity after transfection of the receptor into Slamf8-deficient primary MΦs or RAW 264.7 cells. Upon exposure to bacteria or PMA, protein kinase C activity in Slamf8(-/-) MΦs is increased. This results in an enhanced phosphorylation of p40phox, one key component of the Nox2 enzyme complex, which, in turn, leads to greater Nox2 activity. Taken together, the data show that, in response to inflammation-associated stimuli, the inducible receptor Slamf8 negatively regulates inflammatory responses.

Pubmed ID: 22593622

Authors

  • Wang G
  • Abadía-Molina AC
  • Berger SB
  • Romero X
  • O'Keeffe MS
  • Rojas-Barros DI
  • Aleman M
  • Liao G
  • Maganto-García E
  • Fresno M
  • Wang N
  • Detre C
  • Terhorst C

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Data

June 15, 2012

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI-15066
  • Agency: NIDDK NIH HHS, Id: P30 DK043351
  • Agency: NIAID NIH HHS, Id: R01 AI015066

Mesh Terms

  • Animals
  • Antigens, CD
  • Blotting, Western
  • Cell Line
  • Gene Expression Regulation
  • Inflammation
  • Macrophages
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • NADPH Oxidase
  • Phagosomes
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cell Surface
  • Up-Regulation