Developmental Exposure to Lead Causes Persistent Immunotoxicity in Fischer 344 Rats

Miller, Thomas E.; Golemboski, Karen A.; Ha, R. S.; Bunn, Terry L.; Sanders, F. S.; Dietert, Rodney R.

doi:10.1006/toxs.1998.2424

Cited by 65 publications

(49 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lead levels below those recognized as unsafe have been shown to inhibit production of interferon-γ , a TH 1 immune response, and enhance TH 2 responses [e.g., interleukin (IL)-4, IL-5, IL-10, IL-13, and IgE)] (Annesi-Maesano et al 2003; Miller et al 1998). Results of a laboratory study by Snyder et al (2000) found evidence for maternal transfer of lead both transplacentally and lactationally in pregnant BALB/c mice and their offspring.…”

Section: Discussionmentioning

confidence: 99%

Blood Lead Level and Risk of Asthma

Joseph

Havstad

Ownby

et al. 2005

Environ Health Perspect

View full text Add to dashboard Cite

Asthma and lead poisoning are prevalent among urban children in the United States. Lead exposure may be associated with excessive production of immunoglobulin E, possibly increasing asthma risk and contributing to racial disparities. The objective of this study was to examine racial differences in the association of blood lead level (BLL) to risk of developing asthma. We established and followed a cohort prospectively to determine asthma onset, using patient encounters and drug claims obtained from hospital databases. Participants were managed care enrollees with BLL measured and documented at 1–3 years of age. We used multiple variable analysis techniques to determine the relationship of BLL to period prevalent and incident asthma. Of the 4,634 children screened for lead from 1995 through 1998, 69.5% were African American, 50.5% were male, and mean age was 1.2 years. Among African Americans, BLL ≥5 and BLL ≥10 μg/dL were not associated with asthma. The association of BLL ≥5 μg/dL with asthma among Caucasians was slightly elevated, but not significant [adjusted hazard ratio (adjHR) = 1.4; 95% confidence interval (CI), 0.7–2.9; p = 0.40]. Despite the small number of Caucasians with high BLL, the adjHR increased to 2.7 (95% CI, 0.9–8.1; p = 0.09) when more stringent criteria for asthma were used. When compared with Caucasians with BLL < 5 μg/dL, African Americans were at a significantly increased risk of asthma regardless of BLL (adjHR = 1.4–3.0). We conclude that an effect of BLL on risk of asthma for African Americans was not observed. These results demonstrate the need for further exploration of the complex interrelationships between race, asthma phenotype, genetic susceptibilities, and socioenvironmental exposures, including lead.

show abstract

Section: Discussionmentioning

confidence: 99%

Blood Lead Level and Risk of Asthma

Joseph

Havstad

Ownby

et al. 2005

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…All animal experiments were performed following the guidelines of the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and were approved by the Institutional Animal Care and Use Committee of Hefei University of Technology, China. The method for chronic lead exposure was referred to the previous studies [23], [24]. SD rat dams were randomly divided into two groups: control and lead-exposed group, drinking distilled water and lead water (250 ppm lead acetate in distilled water, 30 ml/day), respectively.…”

Section: Methodsmentioning

confidence: 99%

Developmental Lead Exposure Alters Synaptogenesis through Inhibiting Canonical Wnt Pathway In Vivo and In Vitro

Liu

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

Lead (Pb) exposure has been implicated in the impairment of synaptic plasticity in the developing hippocampus, but the mechanism remains unclear. Here, we investigated whether developmental lead exposure affects the dendritic spine formation through Wnt signaling pathway in vivo and in vitro. Sprague–Dawley rats were exposed to lead throughout the lactation period and Golgi-Cox staining method was used to examine the spine density of pyramidal neurons in the hippocampal CA1 area of rats. We found that lead exposure significantly decreased the spine density in both 14 and 21 days-old pups, accompanied by a significant age-dependent decline of the Wnt7a expression and stability of its downstream protein (β-catenin). Furthermore, in cultured hippocampal neurons, lead (0.1 and 1 µM lead acetate) significantly decreased the spine density in a dose-dependent manner. Exogenous Wnt7a application attenuated the decrease of spine density and increased the stability of the downstream molecules in Wnt signaling pathway. Together, our results suggest that lead has a negative impact on spine outgrowth in the developing hippocampus through altering the canonical Wnt pathway.

show abstract

“…Multiple genetic, life-stage, gender, nutritional, and environmental factors influence the sensitivity to Pb exposure (Bishayi and Sengupta 2006; Bunn et al 2001a, 2001b; Miller et al 1998; Snyder et al 2000). Following Pb exposure, multiple cell types exhibit altered function including macrophages and DCs (Gao, Mondal, and Lawrence 2007; Guo, Mudzinski, and Lawrence 1996; Sengupta and Bishayi 2002).…”

Section: A Specific Example: Lead Exposure Macrophage Function and mentioning

confidence: 99%

Early life environment and developmental immunotoxicity in inflammatory dysfunction and disease

Leifer

Dietert

2011

Toxicological & Environmental Chemistry

View full text Add to dashboard Cite

Components of the innate immune system such as macrophages and dendritic cells are instrumental in determining the fate of immune responses and are, also, among the most sensitive targets of early life environmental alterations including developmental immunotoxicity (DIT). DIT can impede innate immune cell maturation, disrupt tissue microenvironment, alter immune responses to infectious challenges, and disrupt regulatory responses. Dysregulation of inflammation, such as that observed with DIT, has been linked with an increased risk of chronic inflammatory diseases in both children and adults. In this review, we discuss the relationship between early-life risk factors for innate immune modulation and promotion of dysregulated inflammation associated with chronic inflammatory disease. The health risks from DIT-associated inflammation may extend beyond primary immune dysfunction to include an elevated risk of several later-life, inflammatory-mediated diseases that target a wide range of physiological systems and organs. For this reason, determination of innate immune status should be an integral part of drug and chemical safety evaluation.

show abstract

Developmental Exposure to Lead Causes Persistent Immunotoxicity in Fischer 344 Rats

Cited by 65 publications

References 39 publications

Blood Lead Level and Risk of Asthma

Blood Lead Level and Risk of Asthma

Developmental Lead Exposure Alters Synaptogenesis through Inhibiting Canonical Wnt Pathway In Vivo and In Vitro

Early life environment and developmental immunotoxicity in inflammatory dysfunction and disease

Contact Info

Product

Resources

About