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Impact of developmental lead exposure on splenic factors.

ABSTRACT: Lead (Pb) is known to alter the functions of numerous organ systems, including the hematopoietic and immune systems. Pb can induce anemia and can lower host resistance to bacterial and viral infections. The anemia is due to Pb's inhibition of hemoglobin synthesis and Pb's induction of membrane changes, leading to early erythrocyte senescence. Pb also increases B-cell activation/proliferation and skews T-cell help (Th) toward Th2 subset generation. The specific mechanisms for many of the Pb effects are, as yet, not completely understood. Therefore, we performed gene expression analysis, via microarray, on RNA from the spleens of developmentally Pb-exposed mice, in order to gain further insight into these Pb effects. Splenic RNA microarray analysis indicated strong up-regulation of genes coding for proteolytic enzymes, lipases, amylase, and RNaseA. The data also showed that Pb affected the expression of many genes associated with innate immunity. Analysis of the microarray results via GeneSifter software indicated that Pb increased apoptosis, B-cell differentiation, and Th2 development. Direct up-regulation by Pb of expression of the gene encoding the heme-regulated inhibitor (HRI) suggested that Pb can decrease erythropoiesis by blocking globin mRNA translation. Pb's high elevation of digestive/catabolizing enzymes could generate immunogenic self peptides. With Pb's potential to induce new self-peptides and to enhance the expression of caspases, cytokines, and other immunomodulators, further evaluation of Pb's involvement in autoimmune phenomena, especially Th2-mediated autoantibody production, and alteration of organ system activities is warranted.

SUBMITTER: Kasten-Jolly J

PROVIDER: S-EPMC3219921 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Impact of developmental lead exposure on splenic factors.

Kasten-Jolly Jane J Heo Yong Y Lawrence David A DA

Toxicology and applied pharmacology 20100611 2

Lead (Pb) is known to alter the functions of numerous organ systems, including the hematopoietic and immune systems. Pb can induce anemia and can lower host resistance to bacterial and viral infections. The anemia is due to Pb's inhibition of hemoglobin synthesis and Pb's induction of membrane changes, leading to early erythrocyte senescence. Pb also increases B-cell activation/proliferation and skews T-cell help (Th) toward Th2 subset generation. The specific mechanisms for many of the Pb effec ...[more]

PMID: 20542052

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Project description:BackgroundLead (Pb) exposure is associated with adverse neurological development. Most notably, it has been observed through externalizing behavior symptoms, as observed among Inuit children from northern Québec. Evidence for a persistent neurological impact of early Pb exposure later in life is however scarce. Pb exposure may initiate a developmental cascade that increases the risk of long-term behavior problems.ObjectivesTesting for direct associations between childhood Pb concentrations and adolescent externalizing symptoms and substance use, as well as indirect associations through childhood behavior assessments.MethodsThe study sample is a longitudinal cohort of Inuit children (n = 212) followed since birth. Blood Pb concentrations were measured during childhood (median age = 11.4 years) and adolescence (median age = 18.5 years). Externalizing/inattentive behavior were teacher-assessed through the Teacher Report Form and the Disruptive Behavior Disorders Rating Scale for children. At the adolescence follow-up, behavior problems were self-reported by filling Achenbach's Youth Self-Report, the Barkley Adult ADHD-IV Rating Scale, and the Diagnostics Interview Schedule for Children. Adolescent substance use was also self-assessed through the DEP-ADO. Direct and indirect associations of child Pb concentrations with adolescent outcomes were tested through mediation models.ResultsChild blood Pb concentrations were not directly associated with any adolescent outcomes. On the contrary, childhood Pb exposure was indirectly associated, through childhood externalizing behavior assessments, with adolescent externalizing behaviors, binge drinking, and cannabis use. These indirect associations held after controlling for adolescents' concurrent Pb blood concentrations.DiscussionOur results highlight the indirect but lasting effects of child Pb exposure on adolescent behavior problems, and the importance of childhood externalizing behavior in this relationship. Adverse early-life environment put children on a riskier developmental trajectory, increasing their likelihood of lifelong psychological, social and health problems.

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Impact of developmental lead exposure on splenic factors.

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Impact of developmental lead exposure on splenic factors.

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