Adherence of Mouse Peritoneal Macrophages Following Exposure to Lead.

Villanueva, Rosa; Albaladejo, Romana; Ortega, Paloma; Astasio, Paloma; Calle, Marı́a Elisa; Gil, Á.; Granados, B; Domı́nguez-Rojas, Vicente

doi:10.2486/indhealth.35.291

Cited by 6 publications

(4 citation statements)

References 7 publications

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“…Pb has previously been shown to target macrophage function (Sengupta et al, 2002;Song et al, 2001;Villanueva et al, 1997a;Villanueva et al, 1997b) and even NO production by macrophages (Tian et al, 1996;Tian et al, 1995), but never in the context of the immunomodulatory properties of NO.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, others have shown that Pb impairs several aspects of macrophage function including adherence (Villanueva et al, 1997a), chemotaxis (Villanueva et al, 1997b), and clearance of intracellular pathogens (Bishayi et al, 2003;Lawrence, 1981). Interestingly, Pb has also been shown to inhibit nitric oxide (NO) production in myeloid cells such as macrophages (Tian et al, 1996;Tian et al, 1995), and macrophage-derived NO has been reported to suppress allo-T cell proliferation (Hoffman et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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Reduction of myeloid suppressor cell derived nitric oxide provides a mechanistic basis of lead enhancement of alloreactive CD4+ T cell proliferation

Farrer¹,

Hueber²,

Laiosa³

et al. 2008

Toxicology and Applied Pharmacology

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The persistent environmental toxicant and immunomodulator, lead (Pb), has been proposed to directly target CD4 + T cells. However, our studies suggest that CD4 + T cells are an important functional, yet indirect target. In order to identify the direct target of Pb in the immune system and the potential mechanism of Pb-induced immunotoxicity, myeloid suppressor cells (MSCs) were evaluated for their ability to modulate CD4 + T cell proliferation after Pb exposure. Myeloid suppressor cells regulate the adaptive immune response, in part, by inhibiting the proliferation of CD4 + T cells. It is thought that the mechanism of MSC-dependent regulation involves the release of the bioactive gas, nitric oxide (NO), blocking cell signaling cascades downstream of the IL-2 receptor and thus preventing T cells from entering cell-cycle. In mixed lymphocyte culture (MLC), increasing numbers of MSCs suppressed T cell proliferation in a dose-dependent manner, and this suppression is strikingly abrogated with 5 µM lead (Pb) treatment. The Pb-sensitive MSC population is CD11b + , GR1 + and CD11c − and thus phenotypically consistent with MSCs described in other literature. Inhibition of NO-synthase (NOS), the enzyme responsible for the production of NO, enhanced alloreactive T cell proliferation in MLC. Moreover, Pb attenuated NO production in MLC, and exogenous replacement of NO restored suppression in the presence of Pb. Significantly, MSC from iNOS−/− mice were unable to suppress T cell proliferation. An MSC-derived cell line (MSC-1) also suppressed T cell proliferation in MLC, and Pb disrupted this suppression by attenuating NO production. Additionally, Pb disrupted NO production in MSC-1 cells in response to treatment with interferon-γ (IFN-γ) and LPS or in response to concanavalin A-stimulated splenocytes. However, neither the abundance of protein nor levels of mRNA for the inducible isoform of NOS (iNOS) were altered with Pb treatment. Taken together these data suggest that Pb abrogates an MSC-dependent suppression of alloreactive T cell proliferation by inhibiting the function, but not the expression of iNOS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reduction of myeloid suppressor cell derived nitric oxide provides a mechanistic basis of lead enhancement of alloreactive CD4+ T cell proliferation

Farrer¹,

Hueber²,

Laiosa³

et al. 2008

Toxicology and Applied Pharmacology

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“…Earlier research related to immunotoxicity of Pb had served to highlight that many host problems (e.g., neurological, cardiac, renal, reproductive) arising from exposure to Pb may ultimately trace back to Pb-induced changes in myelomonocytic-derived cell population. Pb impairs several aspects of phagocytic cell functions including adherence, chemotaxis [2,3], and clearance of intracellular pathogens [4]. Moreover, Pb has also been shown to inhibit nitric oxide production in both myeloid as well as myeloid suppressor cells [5,6].…”

Section: Introductionmentioning

confidence: 99%

Ubiquitous hazardous metal lead induces TNF-α in human phagocytic THP-1 cells: Primary role of ERK 1/2

Khan

Islam

Sahasrabuddhe

et al. 2011

Journal of Hazardous Materials

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“…Moreover, exposure to Pb, at a concentration of 1300 ppm, was found to inhibit the adherence of murine peritoneal macrophages to plastic tissue culture dishes, which may underpin the inhibitory effects of the metal on the migratory responsiveness of these cells [53,54]. These effects of Pb on the induction of iNOS and spreading of macrophages are opposite to the effects on cytokine production.…”

Section: Leadmentioning

confidence: 75%

Harmful Interactions of Non-Essential Heavy Metals with Cells of the Innate Immune System

Theron¹,

Tintinger²,

Anderson³

2011

J Clin Toxicol

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Adherence of Mouse Peritoneal Macrophages Following Exposure to Lead.

Abstract: Abstract:Lead is a toxin widely used in industry.

Cited by 6 publications

References 7 publications

Reduction of myeloid suppressor cell derived nitric oxide provides a mechanistic basis of lead enhancement of alloreactive CD4+ T cell proliferation

Reduction of myeloid suppressor cell derived nitric oxide provides a mechanistic basis of lead enhancement of alloreactive CD4+ T cell proliferation

Ubiquitous hazardous metal lead induces TNF-α in human phagocytic THP-1 cells: Primary role of ERK 1/2

Harmful Interactions of Non-Essential Heavy Metals with Cells of the Innate Immune System

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