The Epidemiology of Lead Toxicity in Adults: Measuring Dose and Consideration of Other Methodologic Issues

Hu, Howard; Shih, Regina A.; Rothenberg, Stephen J.; Schwartz, Brian S.

doi:10.1289/ehp.9783

Cited by 267 publications

(233 citation statements)

References 104 publications

(136 reference statements)

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“…Additionally, Pb is primarily stored within the mineralized structure of bone where it can remain for decades. During periods of higher bone turnover the toxicokinetic properties of Pb change increasing the potential for the release of Pb back into the blood and re-exposure of soft tissues (Hu, et al 2007). …”

Section: Discussionmentioning

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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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%

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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“…Lead contamination of drinking water supplies can have deleterious effects on multiple organ systems, including the nervous, haematopoietic, renal, endocrine and reproductive systems, especially in children [1][2][3][4][5]. The principal routes of exposure and absorption of lead are through ingestion and inhalation, and around 35% to 50% of lead in drinking water gets absorbed in adults, a figure that can rise to 60% in children [6].…”

Section: Introductionmentioning

confidence: 99%

Drinking water: a major source of lead exposure in Karachi, Pakistan

Ul-Haq¹,

Arain²,

Badar³

et al. 2011

East Mediterr Health J

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Excess lead in drinking water is a neglected source of lead toxicity in Pakistan. A cross-sectional survey in 2007/08 was made of water samples from drinking water sources in Karachi, a large industrial city. This study aimed to compare lead levels between untreated ground water and treated surface (tap) water in 18 different districts. Of 216 ground and surface water samples collected, 86% had lead levels higher than the World Health Organization maximum acceptable concentration of 10 ppb. Mean lead concentration in ground water [146 (SD 119) ppb] was significantly higher than in surface water [77.1 (SD 54) ppb]. None of the 18 districts had a mean lead level of ground or surface water below the WHO cut-off and ground water sources in 9 districts had a severe level of contamination (> 150 ppb). Urgent action is needed to eliminate sources of contamination.

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“…However, BLL measures current exposure to lead, but lead may also be incorporated into bone due to prior exposures not shown in BLL until this bonelead becomes "mobilized" through pregnancy or fracture healing. X-ray fluorescence (XRF) equipment can be used to measure lead concentrations in bones [18] . The standard elevated BLL is above 25 mcg/dL in adults and above 10 mcg/dL in children.…”

Section: Discussionmentioning

confidence: 99%

Extreme gastric dilation caused by chronic lead poisoning: A case report

Begovic¹,

Nozic²,

Kupresanin³

et al. 2008

WJG

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Lead is a toxic metal that affects many organ systems and functions in humans. In the majority of adults, chronic lead poisoning comes from exposures to work places and can occur in numerous work settings, such as manufacturing, lead smelting and refinement, or due to use of batteries, pigments, solder, ammunitions, paint, car radiators, cable and wires, certain cosmetics. In some countries, lead is added to petrol. We present a rare case of gastric dilation caused by long-term petrol ingestion. A 16-year-old young man was admitted to our hospital due to a 6-mo history of exhaustion, dizziness, nausea, abdominal cramps and constipation. X-ray examination revealed dilated stomach descending into the pelvis and small bowel distension. After a long clinical observation, we found that the reason for the chronic lead poisoning of the patient was due to a 3-year history of petrol ingestion. The patient spontaneously recovered and stomach returned to its normal position and size. Lead poisoning should be taken into consideration in all unexplained cases of gastric dilation.

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The Epidemiology of Lead Toxicity in Adults: Measuring Dose and Consideration of Other Methodologic Issues

Cited by 267 publications

References 104 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

Drinking water: a major source of lead exposure in Karachi, Pakistan

Extreme gastric dilation caused by chronic lead poisoning: A case report

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