Enhanced proinflammatory response to endotoxin after priming of macrophages with lead ions.
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.
Flohé
Stefanie B
SB
German Diabetes Research Institute, University of Düsseldorf, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany. flohe@ddfi.uni-duesseldorf.de
Brüggemann
Jutta
J
Herder
Christian
C
Goebel
Carsten
C
Kolb
Hubert
H
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007854:Lead / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism
D016207:Cytokines; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D007854:Lead; C029891:lead chloride; D011493:Protein Kinase C