Modulation of colony-stimulating factor-1 receptors on macrophages by tumor necrosis factor.
The effect of murine rTNF-alpha on the binding of human 125I-rCSF-1 to murine thioglycolate-elicited peritoneal exudate macrophages (PEM) was investigated. At 4 degrees C, 125I-CSF-1 binding to PEM was inhibited by preincubation with human rCSF-1, but not by other cytokines. When PEM were incubated with various cytokines at 37 degrees C, murine rTNF-alpha caused greater than 90% decrease in 125I-CSF-1 binding. This decrease was time, temperature and TNF dose dependent, and was not affected by preincubation with cycloheximide. The reduction in CSF-1-binding activity was reversed by prolonged incubation at 37 degrees C even in the presence of TNF. However, PEM preincubated with TNF subsequently washing free of residual TNF resulted in a rapid recovery of CSF-1 binding. This recovery of CSF-1-binding activity required protein synthesis. Binding studies suggested that the decrease in 125I-CSF-1 binding was most likely caused by a reduction in the number of CSF-1 receptors. In addition, preincubation with TNF at 37 degrees C inhibited 125I-CSF-1 binding on mononuclear phagocytes, including the macrophage cell line J774, bone marrow-derived macrophages, and nonelicited macrophages from three different strains of mice. In contrast, 125I-murine rTNF-alpha binding to PEM was not inhibited by preincubation with CSF-1 at 4 degrees C or 37 degrees C. These data suggest that TNF may play a role in the modulation of receptor expression on blood cells, and may point to a role for this pleiotropic cytokine in the regulation of hemopoiesis.
Shieh
J H
JH
James Ewing Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York 10021.
Peterson
R H
RH
Warren
D J
DJ
Moore
M A
MA
D000818:Animals; D001202:Ascitic Fluid; D003115:Colony-Stimulating Factors / Q000378:metabolism* / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000378:metabolism* / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007700:Kinetics; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D013696:Temperature; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007375:Interleukin-1; D007457:Iodine Radioisotopes; D008233:Lymphotoxin-alpha; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003513:Cycloheximide