A Heterocomplex Formed by the Calcium-binding Proteins MRP8 (S100A8) and MRP14 (S100A9) Binds Unsaturated Fatty Acids with High Affinity

Siegenthaler, Georges; Roulin, Karen; Chatellard-Gruaz, Dominique; Hotz, Raymonde; Saurat, J.‐H.; Hellman, Ulf; Hagens, Gerry

doi:10.1074/jbc.272.14.9371

Cited by 88 publications

(73 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S100A8 is hydrophobic and interacts with unsaturated fatty acids (11). S100A8/A9 binds cytosolic p67 phox via S100A8 and delivers arachidonic acid, a positive regulator of NADPH oxidase (53).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

S-Nitrosylated S100A8: Novel Anti-Inflammatory Properties

Lim

Raftery

Cai

et al. 2008

The Journal of Immunology

111

106

View full text Add to dashboard Cite

S100A8 and S100A9, highly expressed by neutrophils, activated macrophages, and microvascular endothelial cells, are secreted during inflammatory processes. Our earlier studies showed S100A8 to be an avid scavenger of oxidants, and, together with its dependence on IL-10 for expression in macrophages, we postulated that this protein has a protective role. S-nitrosylation is an important posttranslational modification that regulates NO transport, cell signaling, and homeostasis. Relatively few proteins are targets of S-nitrosylation. To date, no inflammation-associated proteins with NO-shuttling capacity have been identified. We used HPLC and mass spectrometry to show that S100A8 and S100A9 were readily S-nitrosylated by NO donors. S-nitrosylated S100A8 (S100A8-SNO) was the preferred nitrosylated product. No S-nitrosylation occurred when the single Cys residue in S100A8 was mutated to Ala. S100A8-SNO in human neutrophils treated with NO donors was confirmed by the biotin switch assay. The stable adduct transnitrosylated hemoglobin, indicating a role in NO transport. S100A8-SNO suppressed mast cell activation by compound 48/80; intravital microscopy was used to demonstrate suppression of leukocyte adhesion and extravasation triggered by compound 48/80 in the rat mesenteric microcirculation. Although S100A8 is induced in macrophages by LPS or IFN-γ, the combination, which activates inducible NO synthase, did not induce S100A8. Thus, the antimicrobial functions of NO generated under these circumstances would not be compromised by S100A8. Our results suggest that S100A8-SNO may regulate leukocyte-endothelial cell interactions in the microcirculation, and suppression of mast cell-mediated inflammation represents an additional anti-inflammatory property for S100A8.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The noncovalent heterocomplex, known as calprotectin, is an intracellular transporter of unsaturated fatty acids (11). Calprotectin regulates NADPH oxidase complex assembly and calcium-dependent signaling during phagocyte activation (12), and microtubule reorganization during leukocyte migration (13).…”

mentioning

confidence: 99%

S-Nitrosylated S100A8: Novel Anti-Inflammatory Properties

Lim

Raftery

Cai

et al. 2008

The Journal of Immunology

111

106

View full text Add to dashboard Cite

show abstract

“…Several reports suggest that S100A8/A9 inhibits bacterial and fungal growth by zinc chelation and depletion of zinc, a necessary component of microbial growth (20, 24, 25, 46 -48). Furthermore, the proteins bind arachidonic acid, and depletion of arachidonic acid has also been suggested as a mechanism of bacterial growth inhibition (49,50). Observations suggesting that S100A8/A9 contributes to mucosal innate immunity are that the complex inhibits invasion of epithelial cells by bacterial pathogens (51), and a recent study showing that S100A9 is crucial for keratinocyte resistance to invasion by Listeria monocytogenes and Salmonella typhimurium (52).…”

Section: Discussionmentioning

confidence: 99%

Bacterial Surface Protein L Binds and Inactivates Neutrophil Proteins S100A8/A9

Åkerström

Björck

2009

The Journal of Immunology

View full text Add to dashboard Cite

Finegoldia magna is an anaerobic bacterial species that is part of the normal human flora on all nonsterile body surfaces, but it is also a significant opportunistic pathogen causing a wide range of infections. Some isolates of F. magna that are more frequently associated with clinical infection express protein L, a surface protein containing multiple homologous domains (B1-B5) that bind Igs through interactions with Ig L chains. The present study shows that the N-terminal A domain of protein L binds S100A8/A9, antibacterial proteins present in large amounts in the cytoplasm of neutrophils, but also extracellularly in tissues during inflammation. As a result, protein L-expressing F. magna are protected against killing by S100A8/A9. Igs and S100A8/A9 were found to interact independently with protein L, demonstrating that this bacterial surface protein is capable of manipulating both adaptive and innate immune defense mechanisms.

show abstract

“…acid in a calcium-dependent manner, whereas the S100A8 or S100A9 homodimers lack this property [6][7][8]. Data obtained through different experimental approaches suggest that arachidonic acid is an in vivo activator of the NADPH oxidase.…”

Section: Discussionmentioning

confidence: 99%

“…The S100A8/A9 protein might also serve as a reservoir and a carrier of arachidonic acid [6][7][8]. This latter finding is all the more noteworthy as arachidonic acid is currently used in cell-free system to activate the O 2 -generating NADPH oxidase, an enzymatic complex responsible for the microbicidal function of neutrophils and macrophages [9].…”

mentioning

confidence: 99%

The S100A8/A9 protein as a partner for the cytosolic factors of NADPH oxidase activation in neutrophils

Doussière

Bouzidi

Vignais

2002

European Journal of Biochemistry

View full text Add to dashboard Cite

In a previous study, the S100A8/A9 protein, a Ca 2+ -and arachidonic acid-binding protein, abundant in neutrophil cytosol, was found to potentiate the activation of the redox component of the O 2 -generating oxidase in neutrophils, namely the membrane-bound flavocytochrome b, by the cytosolic phox proteins p67phox, p47phox and Rac (Doussie`re J., Bouzidi F. and Vignais P.V. (2001) Biochem. Biophys. Res. Commun. 285, 1317-1320. This led us to check by immunoprecipitation and protein fractionation whether the cytosolic phox proteins could bind to S100A8/A9. Following incubation of a cytosolic extract from nonactivated bovine neutrophil with protein A-Sepharose bound to antip67phox antibodies, the recovered immunoprecipitate contained the S100 protein, p47phox and p67phox. Cytosolic protein fractionation comprised two successive chromatographic steps on hydroxyapatite and DEAE cellulose, followed by isoelectric focusing. The S100A8/A9 heterodimeric protein comigrated with the cytosolic phox proteins, and more particularly with p67phox and Rac2, whereas the isolated S100A8 protein displayed a tendancy to bind to p47phox. Using a semirecombinant cell-free system of oxidase activation consisting of recombinant p67phox, p47phox and Rac2, neutrophil membranes and arachidonic acid, we found that the S100A8/A9-dependent increase in the elicited oxidase activity corresponded to an increase in the turnover of the membrane-bound flavocytochrome b, but not to a change of affinity for NADPH or O 2 . In the absence of S100A8/A9, oxidase activation departed from michaelian kinetics above a critical threshold concentration of cytosolic phox proteins. Addition of S100A8/A9 to the cell-free system rendered the kinetics fully michaelian. The propensity of S100A8/A9 to bind the cytosolic phox proteins, and the effects of S100A8/A9 on the kinetics of oxidase activation, suggest that S100A8/A9 might be a scaffold protein for the cytosolic phox proteins or might help to deliver arachidonic acid to the oxidase, thus favoring the productive interaction of the cytosolic phox proteins with the membrane-bound flavocytochrome b.Keywords: NADPH oxidase activation; superoxide O 2 -; neutrophils; phox proteins; S100A8/ A9 protein.The heterodimeric Ca 2+ -binding protein S100A8/A9, also referred to in the literature as MRP8/MRP14, is expressed constitutively in large amounts in neutrophils and monocytes [1][2][3], where it plays a role in the activation process (reviewed in [4]) and adhesion [5]. The S100A8/A9 protein might also serve as a reservoir and a carrier of arachidonic acid [6][7][8]. This latter finding is all the more noteworthy as arachidonic acid is currently used in cell-free system to activate the O 2 -generating NADPH oxidase, an enzymatic complex responsible for the microbicidal function of neutrophils and macrophages [9]. In its activated form, the NADPH oxidase complex is composed of a membranebound flavocytochrome b and proteins of cytosolic origin, called phox (for phagocyte oxidase) factors of oxidase activation or cytosolic...

show abstract

A Heterocomplex Formed by the Calcium-binding Proteins MRP8 (S100A8) and MRP14 (S100A9) Binds Unsaturated Fatty Acids with High Affinity

Cited by 88 publications

References 36 publications

S-Nitrosylated S100A8: Novel Anti-Inflammatory Properties

S-Nitrosylated S100A8: Novel Anti-Inflammatory Properties

Bacterial Surface Protein L Binds and Inactivates Neutrophil Proteins S100A8/A9

The S100A8/A9 protein as a partner for the cytosolic factors of NADPH oxidase activation in neutrophils

Contact Info

Product

Resources

About