IFN-gamma enhances sensitivity of human macrophages to extracellular ATP-mediated lysis.
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.
University of South Florida College of Medicine, Department of Medical Microbiology and Immunology, Tampa 33612.
D K
DK
Blanchard
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McMillen
J Y
JY
Djeu
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008264:Macrophages / Q000187:drug effects*
D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000255:Adenosine Triphosphate