Lead toxicity via arachidonate signal transduction to growth responses in the splenic macrophage.
Lead chloride modulated the macrophage cell surface growth signal-transduced, lipid second messenger prostaglandin E2 (PGE2), concomitant with cell differentiation. In virgin macrophage, PGE2 was increased by lead in a dose-dependent manner, suggesting suppression of the immune function (inversely regulated by PGE2). Upon stimulation by bacterial endotoxin, lead-treated cells displayed decreased PGE2 with immune augmentation as tested by zymosan particle ingestion. These effects were simulated by a glutathione synthesis inhibitor around 10 microM lead, and by cycloheximide around 50 microM lead, suggesting a mechanism similar to viral infection.
Lee
J J
JJ
Department of Microbiology and Immunology, Albany Medical College, Union University, New York 12208.
Battles
A H
AH
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D019328:Buthionine Sulfoximine; D003513:Cycloheximide / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D007854:Lead / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D008070:Lipopolysaccharides; D008717:Methionine Sulfoximine; D016718:Arachidonic Acid; D007854:Lead; D019328:Buthionine Sulfoximine; D003513:Cycloheximide; D015232:Dinoprostone