Lead Toxicity via Arachidonate Signal Transduction to Growth Responses in the Splenic Macrophage

• Published in: Environmental research Vol. 67; no. 2; pp. 209 - 219
• Main Authors: Lee, J.J., Battles, A.H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.11.1994; Elsevier
• Subjects: Animals; Arachidonic Acid - metabolism; Biological and medical sciences; Buthionine Sulfoximine; Chemical and industrial products toxicology. Toxic occupational diseases; Cycloheximide - pharmacology; Dinoprostone - metabolism; Lead - toxicity; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Medical sciences; Metals and various inorganic compounds; Methionine Sulfoximine - analogs & derivatives; Methionine Sulfoximine - pharmacology; Mice; Signal Transduction; Spleen - cytology; Spleen - drug effects; Spleen - metabolism; Toxicology; Immunopathology; Toxicity; Arachidonic acid derivatives; Major histocompatibility system; Cytokine; Prostaglandin E2; In vitro; Heavy metal; Signal transduction; Lead; Mechanism of action; Phagocytosis; Macrophage
• ISSN: 0013-9351; 1096-0953
• DOI: 10.1006/enrs.1994.1075

Lead chloride modulated the macrophage cell surface growth signal-transduced, lipid second messenger prostaglandin E 2 (PGE 2), concomitant with cell differentiation. In virgin macrophage, PGE 2 was increased by lead in a dose-dependent manner, suggesting suppression of the immune function (inversely regulated by PGE 2). Upon stimulation by bacterial endotoxin, lead-treated cells displayed decreased PGE 2 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.