Monokine mediated release of intracellular iron in tumor target cells in vitro

Activated macrophages cocultured with tumor cells mediate intracellular iron release in both lytically-sensitive and lytically-resistant targets. The early inhibition of aconitase and loss of intracellular iron in tumor targets upon coincubation with activated macrophages have been proposed to be causally linked. In this report we demonstrate that release of iron may be monokine mediated. The monokine is rapidly released from murine BCG-activated peritoneal macrophages after endotoxin triggering, reaching peak levels in the supernatant within 2-4 hr. The response of the target depends on both the dose of the monokine administered and the duration of its exposure. The monokine is heat-labile and is retained by ultrafiltration on a YM-10 membrane. Iron-release is not mediated by a cytolytic factor secreted by activated macrophages, nor by a factor which causes reversible lesions in the electron transport chain. The molecular weight of the iron-releasing monokine is approximately 50 kD as determined by HPLC gel filtration on Superose 12.