Effects of heavy metal ions on phospholipid metabolism in human neutrophils: relationship to ionophore-mediated cytotoxicity.
This study examined the effects of 0.1mM heavy metal ions (Au3+, Zn2+, Cr3+, Mn2+, and Cu2+) on ionophore-treated human neutrophils. Treatment of human neutrophils with 5-10 microM ionophore A23187 resulted in phospholipid deacylation and eicosanoid release within 5 min. After approximately 20 min, viability decreased significantly with near total cell death by 50 min. Heavy metal ions altered phospholipid metabolism, eicosanoid synthesis, and cytotoxicity in parallel fashion. Radioimmunoassays for 5-HETE and LTB4 demonstrated that Au3+ and Zn2+ stimulated, Cr3+ had little effect on, and Mn2+ and Cu2+ inhibited eicosanoid release from ionophore-treated neutrophils. Cells prelabelled with [3H]arachidonic acid exhibited similar metal-mediated effects on lipid metabolism. Strong negative correlations between metal effects on viability and the metabolism of arachidonic acid suggest that eicosanoids participate in ionophore-induced cytotoxicity.
D001095:Arachidonic Acids / Q000097:blood; D000001:Calcimycin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D008670:Metals / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism*; D010743:Phospholipids / Q000097:blood*
D001095:Arachidonic Acids; D008670:Metals; D010743:Phospholipids; D000001:Calcimycin