Improvement of human dendritic cell culture for immunotoxicological investigations

Hymery, Nolwenn; Sibiril, Y.; Parent‐Massin, D.

doi:10.1007/s10565-006-0180-3

Cited by 21 publications

(9 citation statements)

References 20 publications

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“…It has also been established that vanadium is detrimental to the immune function by simply decreasing immune cell numbers in peripheral blood (Hogan 2000;Di Gioacchino et al 2002). As several studies have already focused on the effects of vanadium on the T-lymphocyte, it was apparent to investigate the influence of vanadium on DC, which are important in initiating and driving an adaptive immune response (Hymery, Sibiril, and Parent-Massin 2006). …”

Section: Discussionmentioning

confidence: 99%

Effect of vanadium on human dendritic cells

Chan

Filgueira

2010

Toxicological & Environmental Chemistry

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Vanadium is a heavy metal that has no known biological role in humans. However, increasing exposure through advances in medical applicationsorthodontic/orthopedic metal implants, vanadium-containing drugs and environmental exposure have raised questions on the influence of vanadium on the immune system. As initiators of the adaptive immune response, dendritic cells (DC) are responsible for the differentiation of effector T-lymphocytes and the resulting immune reactivity. This study assessed the differences in immune reactivity towards various vanadium compounds and investigated the influence of vanadium (III), (IV), and (V) ions on peripheral blood monocytes (PBMC) and DC. Exposure to vanadium (III) and (IV) concentrations above 125 mM reduced the proliferation of lymphocytes. Mitochondrial DC activity was reduced in the presence of low concentrations of vanadium. Flow cytometry analysis of cell surface molecules showed slight alterations of MHC class II (antigen presenting molecule) and reduction of CD54 (adhesion molecule) with increasing vanadium concentrations. Secreted cytokines and chemokines produced by DC were measured through a cytometric bead assay, which showed no significant difference after exposure to various vanadium ions. Finally, the ability of vanadium-treated DC to interact with lymphocytes was measured through proliferation of allogenic non-adherent PBMC and showed retention of proliferative capacity. These results indicate that vanadium exerts a weak influence on the maturation and function of DC, which suggests that alterations in immune reactivity by vanadium is mediated directly on effector lymphocytes.

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Section: Discussionmentioning

confidence: 99%

Effect of vanadium on human dendritic cells

Chan

Filgueira

2010

Toxicological & Environmental Chemistry

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“…To the authors’ knowledge, this is the first report to demonstrate the immunotoxic effects of DA in any mammalian species. Previous reports demonstrated that DA was not immunotoxic either upon i n vitro exposure of isolated human dendritic cells [ 28 ] or rats exposed in vivo [ 29 ], although different cell types and route of exposure were employed. When exposed to physiologically relevant concentrations of DA, different responses were observed between in vivo and in vitro exposure.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effects of Domoic Acid Differ Between In vivo and In vitro Exposure in Mice

et al. 2008

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Abstract:The immunotoxic potential of domoic acid (DA), a well-characterized neurotoxin, has not been fully investigated. Phagocytosis and lymphocyte proliferation were evaluated following in vitro and in vivo exposure to assay direct vs indirect effects. Mice were injected intraperitoneally with a single dose of DA (2.5 µg/g b.w.) and sampled after 12, 24, or 48 hr. In a separate experiment, leukocytes and splenocytes were exposed in vitro to 0, 1, 10, or 100 µM DA. In vivo exposure resulted in a significant increase in monocyte phagocytosis (12-hr), a significant decrease in neutrophil phagocytosis (24-hr), a significant decrease in monocyte phagocytosis (48-hr), and a significant reduction in T-cell mitogen-induced lymphocyte proliferation (24-hr). In vitro exposure significantly reduced neutrophil and monocyte phagocytosis at 1 µM. B-and T-cell mitogen-induced lymphocyte proliferation were both significantly increased at 1 and 10 µM, and significantly decreased at 100 µM. Differences between in vitro and in vivo results suggest that DA may exert its immunotoxic effects both directly and indirectly. Modulation of cytosolic calcium suggests that DA exerts its effects through ionotropic glutamate subtype surface receptors at least on monocytes. This study is the first to identify DA as an immunotoxic chemical in a mammalian species.

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“…Therefore, based on the prototypical phenotypic and functional changes that result from the presence of potent maturational stimuli, JAWSII DC can be used as an experimental model to study the in vitro effects of atrazine and other immunotoxicants on the DC maturation process. There are ongoing efforts to improve and standardize primary DC cultures for immunotoxicity research, including human DC (Hymery et al 2006a). Primary DC cultures have been used successfully for the assessment of the effects of trichothecenes (Hymery et al 2006b) and PAHs (Laupeze et al 2002) on DC.…”

Section: Discussionmentioning

confidence: 99%

In vitro atrazine exposure affects the phenotypic and functional maturation of dendritic cells

Pinchuk

Lee

Filipov

2007

Toxicology and Applied Pharmacology

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Recent data suggest that some of the immunotoxic effects of the herbicide atrazine, a very widely used pesticide, may be due to perturbations in dendritic cell (DC) function. As consequences of atrazine exposure on the phenotypic and functional maturation of DC have not been studied, our objective was, using the murine DC line, JAWSII, to determine whether atrazine will interfere with DC maturation. First, we characterized the maturation of JAWSII cells in vitro by inducing them to mature in the presence of growth factors and selected maturational stimuli in vitro. Next, we exposed the DC cell line to a concentration range of atrazine and examined its effects on phenotypic and functional maturation of DC. Atrazine exposure interfered with the phenotypic and functional maturation of DC at non-cytotoxic concentrations. Among the phenotypic changes caused by atrazine exposure was a dose-dependent removal of surface MHC-I with a significant decrease being observed at 1 microM concentration. In addition, atrazine exposure decreased the expression of the costimulatory molecule CD86 and it downregulated the expression of the CD11b and CD11c accessory molecules and the myeloid developmental marker CD14. When, for comparative purposes, we exposed primary thymic DC to atrazine, MHC-I and CD11c expression was also decreased. Phenotypic changes in JAWSII DC maturation were associated with functional inhibition of maturation as, albeit at higher concentrations, receptor-mediated antigen uptake was increased by atrazine. Thus, our data suggest that atrazine directly targets DC maturation and that toxicants such as atrazine that efficiently remove MHC-I molecules from the DC surface are likely to contribute to immune evasion.

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Improvement of human dendritic cell culture for immunotoxicological investigations

Cited by 21 publications

References 20 publications

Effect of vanadium on human dendritic cells

Effect of vanadium on human dendritic cells

Immunomodulatory Effects of Domoic Acid Differ Between In vivo and In vitro Exposure in Mice

In vitro atrazine exposure affects the phenotypic and functional maturation of dendritic cells

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