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German Diabetes Research Institute, University of Düsseldorf, Germany
Correspondence: Dr. Stefanie B. Flohé, German Diabetes Research Institute, Aufm Hennekamp 65, 40225 Düsseldorf, Germany. E-mail: flohe{at}ddfi.uni-duesseldorf.de
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 (BMM
) 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-
(TNF-
),
interleukin (IL)-6, IL-12, and prostaglandin E2
(PGE2) 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-
and IL-6 release. In conclusion, lead ions prime
BMM
for enhanced proinflammatory cytokine secretion in response to
LPS, likely by activation of protein kinase C and subsequent synthesis
of an unidentified mediator.
Key Words: heavy metals LPS cytokines
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