title: Cutting edge: Slamf8 is a negative regulator of Nox2 activity in macrophages.
abstract: 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.
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Wang
authors.forename: Ana C
authors.initials: AC
authors.lastname: Abadía-Molina
authors.forename: Scott B
authors.initials: SB
authors.lastname: Berger
authors.forename: Xavier
authors.initials: X
authors.lastname: Romero
authors.forename: Michael S
authors.initials: MS
authors.lastname: O'Keeffe
authors.forename: Domingo I
authors.initials: DI
authors.lastname: Rojas-Barros
authors.forename: Marta
authors.initials: M
authors.lastname: Aleman
authors.forename: Gongxian
authors.initials: G
authors.lastname: Liao
authors.forename: Elena
authors.initials: E
authors.lastname: Maganto-García
authors.forename: Manuel
authors.initials: M
authors.lastname: Fresno
authors.forename: Ninghai
authors.initials: N
authors.lastname: Wang
authors.forename: Cynthia
authors.initials: C
authors.lastname: Detre
authors.forename: Cox
authors.initials: C
authors.lastname: Terhorst
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D005786:Gene Expression Regulation / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000276:immunology / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases