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J Leukoc Biol. 2002 Mar;71(3):417-24.

Enhanced proinflammatory response to endotoxin after priming of macrophages with lead ions.

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German Diabetes Research Institute, University of Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.


Exposure to lead ions strongly enhances the susceptibility of rodents to endotoxin shock and parasitical infections. Macrophages play a key role during the immune response to lipopolysaccharide (LPS) and during the defense against parasites and might be a target of lead. In the present study, bone marrow-derived macrophages (BMMphi) pretreated with lead chloride prior to stimulation with LPS were analyzed for their release of immune mediators. Lead-pretreated cells released up to tenfold increased amounts of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-12, and prostaglandin E(2) (PGE(2)) but less IL-10 compared with controls. These effects were paralleled by enhanced mRNA levels and were dependent on the duration of lead pretreatment. Inhibition of protein kinase C or of protein synthesis during the priming phase blocked the lead-induced increase of TNF-alpha and IL-6 release. In conclusion, lead ions prime BMMphi for enhanced proinflammatory cytokine secretion in response to LPS, likely by activation of protein kinase C and subsequent synthesis of an unidentified mediator.

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