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 simulatable by a glutathione synthesis inhibitor around 10 μM lead, and by cycloheximide around 50 μM lead, suggesting a mechanism similar to viral infection.