IL-2 enhances c-fms expression in human monocytes

• Published in: The Journal of immunology (1950) Vol. 145; no. 4; pp. 1137 - 1143
• Main Authors: Espinoza-Delgado, I, Longo, DL, Gusella, GL, Varesio, L
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.08.1990; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; c-fms; Colony-Stimulating Factors - pharmacology; Cytotoxicity, Immunologic - drug effects; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression - drug effects; genes; Humans; Immunobiology; Interferon-gamma - pharmacology; Interleukin-2 - pharmacology; Lymphokines, interleukins ( function, expression); Macrophage Colony-Stimulating Factor; monocytes; Monocytes - drug effects; Monocytes - immunology; Proto-Oncogene Proteins - analysis; Proto-Oncogene Proteins - genetics; Proto-Oncogenes; Receptor, Macrophage Colony-Stimulating Factor; Regulatory factors and their cellular receptors; RNA, Messenger - analysis; Human; Messenger RNA; Interleukin 2; Monocyte; C-Onc gene; Cytokine; Activation; Macrophage colony stimulating factor; Gene expression; Mechanism; Protooncogene; Biological receptor
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.145.4.1137

We investigated the effects of IL-2 and IFN-gamma on the expression of the proto-oncogene c-fms mRNA, which encodes for the macrophage CSF receptor. Low constitutive expression of c-fms mRNA was detected in fresh human monocytes. Stimulation of monocytes with IL-2 induced a significant increase in c-fms mRNA relative to medium control that was observed as early as 6 h after IL-2 stimulation. Dose-response experiments showed that 100 U/ml of IL-2 were sufficient to enhance the expression of c-fms mRNA. In contrast, IFN-gamma did not modify the levels of c-fms transcript. Immunoprecipitation experiments demonstrated that IL-2 enhanced c-fms glycoprotein levels. Experiments in which monocytes were activated with IFN-gamma or IL-2 followed by macrophage CSF-1 and then tested for tumoricidal activity demonstrated that macrophage CSF-1 sustained the cytotoxic activity induced by IL-2 but not by IFN-gamma. These data demonstrate that IL-2 enhances c-fms mRNA and c-fms glycoprotein expression suggesting that IL-2, by augmenting expression of macrophage CSF-1 receptors, can lead to prolongation of monocyte-mediated tumoricidal activity obtained in the presence of exogenous macrophage CSF-1.