Reactive oxygen species activate human peripheral blood dendritic cells

Rutault, Karine; Alderman, Charles; Chain, Benjamin M.; Katz, David R.

doi:10.1016/s0891-5849(98)00194-4

Cited by 183 publications

(110 citation statements)

References 15 publications

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“…It was also demonstrated that the redox imbalance induced by skin sensitizers is important in the regulation of DC functions [5,38,39,41,47,61]. Therefore, the increase in Trx-1 mRNA expression observed in .…”

Section: Discussionmentioning

confidence: 96%

Effect of lipopolysaccharide, skin sensitizers and irritants on thioredoxin-1 expression in dendritic cells: relevance of different signalling pathways

et al. 2009

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Thioredoxin-1 is a ubiquitous protein involved in phenotypical and functional changes in dendritic cells (DC). We investigated the eVect of lipopolysaccharide (LPS), skin sensitizers, and irritants on thioredoxin-1 by Western blot and immunoXuorescence and on mRNA by real-time PCR. As DC models, we used a skin DC line and DC derived from human blood monocytes. We observed that all tested chemicals increased thioredoxin-1 expression, which is only transient for irritants, being the strongest eVect observed for LPS (63 § 15%). To address the involvement of thioredoxin-1 in DC maturation, we analysed the eVect of an activator of thioredoxin-1 expression, hydrogen peroxide, on CD86 expression, a marker of DC maturation. We found that hydrogen peroxide increases thioredoxin-1 and CD86 expression reinforcing thioredoxin-1 involvement in DC maturation. Because mitogen-activated protein kinases and PI3K are activated upon DC maturation, we also analysed their involvement in thioredoxin-1 modulation. We veriWed that LPS-induced upregulation of thioredoxin-1 expression was dependent on PI3K pathway.

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Section: Discussionmentioning

confidence: 96%

Effect of lipopolysaccharide, skin sensitizers and irritants on thioredoxin-1 expression in dendritic cells: relevance of different signalling pathways

et al. 2009

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“…These data reveal that covalent binding of sulfamethoxazole metabolites to viable dendritic cells is associated with increased CD40 expression. It is worth mentioning that the association between bioactivation and CD40 up-regulation is not necessarily due to covalent binding: auto-oxidative conversion of SMX-NHOH to SMX-NO can generate reactive oxygen species and oxidative stress (68), both known inducers of dendritic cell maturation (69,70).…”

Section: Discussionmentioning

confidence: 99%

Sulfamethoxazole and Its Metabolite Nitroso Sulfamethoxazole Stimulate Dendritic Cell Costimulatory Signaling

Sanderson

Naisbitt

Farrell

et al. 2007

The Journal of Immunology

117

107

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Different signals in addition to the antigenic signal are required to initiate an immunological reaction. In the context of sulfamethoxazole allergy, the Ag is thought to be derived from its toxic nitroso metabolite, but little is known about the costimulatory signals, including those associated with dendritic cell maturation. In this study, we demonstrate increased CD40 expression, but not CD80, CD83, or CD86, with dendritic cell surfaces exposed to sulfamethoxazole (250–500 μM) and the protein-reactive metabolite nitroso sulfamethoxazole (1–10 μM). Increased CD40 expression was not associated with apoptosis or necrosis, or glutathione depletion. Covalently modified intracellular proteins were detected when sulfamethoxazole was incubated with dendritic cells. Importantly, the enzyme inhibitor 1-aminobenzotriazole prevented the increase in CD40 expression with sulfamethoxazole, but not with nitroso sulfamethoxazole or LPS. The enzymes CYP2C9, CYP2C8, and myeloperoxidase catalyzed the conversion of sulfamethoxazole to sulfamethoxazole hydroxylamine. Myeloperoxidase was expressed at high levels in dendritic cells. Nitroso sulfamethoxazole immunogenicity was inhibited in mice with a blocking anti-CD40L Ab. In addition, when a primary nitroso sulfamethoxazole-specific T cell response using drug-naive human cells was generated, the magnitude of the response was enhanced when cultures were exposed to a stimulatory anti-CD40 Ab. Finally, increased CD40 expression was 5-fold higher on nitroso sulfamethoxazole-treated dendritic cells from an HIV-positive allergic patient compared with volunteers. These data provide evidence of a link between localized metabolism, dendritic cell activation, and drug immunogenicity.

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“…In DC, oxygen radicals were implicated in both DC differentiation (43) and maturation (26,27) and in IL-8/CXCL8 production (24,25). Controversial data are present in the literature about the inhibitory action (52) or the positive role (26,53) of oxygen radicals on the ability of DC to stimulate T cell response.…”

Section: Discussionmentioning

confidence: 99%

Toll Receptor-Mediated Regulation of NADPH Oxidase in Human Dendritic Cells

Vulcano

Dusi

Lissandrini

et al. 2004

The Journal of Immunology

122

108

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Activation of NADPH oxidase represents an essential mechanism of defense against pathogens. Dendritic cells (DC) are phagocytic cells specialized in Ag presentation rather than in bacteria killing. Human monocyte-derived DC were found to express the NADPH oxidase components and to release superoxide anions in response to phorbol esters and phagocytic agonists. The NADPH oxidase components p47phox and gp91phox were down-regulated during monocyte differentiation to DC, and maturation of DC with pathogen-derived molecules, known to activate TLRs, increased p47phox and gp91phox expression and enhanced superoxide anions release. Similar results were obtained with plasmacytoid DC following maturation with influenza virus. In contrast, activation of DC by immune stimuli (CD40 ligand) did not regulate NADPH oxidase components or respiratory burst. NADPH oxidase-derived oxygen radicals did not play any role in DC differentiation, maturation, cytokine production, and induction of T cell proliferation, as based on the normal function of DC generated from chronic granulomatous disease patients and the use of an oxygen radical scavenger. However, NADPH oxidase activation was required for DC killing of intracellular Escherichia coli. It is likely that the selective regulation of oxygen radicals production by pathogen-activated DC may function to limit pathogen dissemination during DC trafficking to secondary lymphoid tissues.

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Reactive oxygen species activate human peripheral blood dendritic cells

Cited by 183 publications

References 15 publications

Effect of lipopolysaccharide, skin sensitizers and irritants on thioredoxin-1 expression in dendritic cells: relevance of different signalling pathways

Effect of lipopolysaccharide, skin sensitizers and irritants on thioredoxin-1 expression in dendritic cells: relevance of different signalling pathways

Sulfamethoxazole and Its Metabolite Nitroso Sulfamethoxazole Stimulate Dendritic Cell Costimulatory Signaling

Toll Receptor-Mediated Regulation of NADPH Oxidase in Human Dendritic Cells

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