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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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1
German Diabetes Research Institute, University of Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany. flohe@ddfi.uni-duesseldorf.de

Abstract

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.

PMID:
11867679
[Indexed for MEDLINE]
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