The Journal of Immunology, Vol 147, Issue 8 2579-2585, Copyright © 1991 by American Association of Immunologists

ARTICLES

IFN-gamma enhances sensitivity of human macrophages to extracellular ATP-mediated lysis

DK Blanchard, S McMillen and JY Djeu
University of South Florida College of Medicine, Department of Medical Microbiology and Immunology, Tampa 33612.

In an effort to determine the mechanism by which autologous monocytes are killed by lymphokine-activated killer cells, soluble mediators were examined for their direct effect on target cells. Extracellular ATP (ATPo), but not ADP, was found to lyse human culture-derived macrophages in a 6-h 51Cr-release assay. Treatment of monocytes with human rIFN-gamma rendered those cells significantly more sensitive to ATPo compared to untreated or granulocyte-macrophage CSF-(GM-CSF) treated cells. In addition, IFN-gamma-treated macrophages released approximately 80% of 51Cr label within 15 min after the addition of ATPo, whereas GM-CSF-treated cells did not release significant levels of radiolabel until 4 to 6 h after initial stimulation with ATPo. Time course studies also demonstrated that 3 days of incubation of macrophages with IFN-gamma induced optimal sensitivity to ATPo, although some effect was noted after 4 h of incubation. Thus, IFN-gamma treatment of macrophages elicited increased sensitivity to ATPo- mediated lysis, a phenomenon characterized by rapid release of 51Cr from labeled cells and which is possibly due to induction or activation of surface ATP-binding receptors different from those present on GM-CSF- treated or untreated macrophages.

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