Induction of Macrophage Tumoricidal Activity by Granulocyte-Macrophage Colony-Stimulating Factor

• Published in: Science (American Association for the Advancement of Science) Vol. 232; no. 4749; pp. 506 - 508
• Main Authors: Grabstein, Kenneth H., Urdal, David L., Tushinski, Robert J., Mochizuki, Diane Y., Price, Virginia L., Cantrell, Michael A., Gillis, Steven, Conlon, Paul J.
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 25-04-1986; American Association for the Advancement of Science
• Subjects: B lymphocytes; Biological and medical sciences; Blood; Cell Line; Cell lines; Colony stimulating factors; Colony-Stimulating Factors - biosynthesis; Colony-Stimulating Factors - pharmacology; Complementary DNA; Cultured cells; Cytotoxicity, Immunologic - drug effects; Host-tumor relations. Immunology. Biological markers; Humans; Immunologic research; Immunological research; Interferon-gamma - biosynthesis; Interferon-gamma - pharmacology; Macrophages; Macrophages - drug effects; Medical sciences; Melanoma - immunology; Monocytes; Monocytes - drug effects; Neoplasms - immunology; Recombinant Proteins - biosynthesis; Recombinant Proteins - pharmacology; T lymphocytes; Tumors; Yeasts; Human; Cell culture; Malignant melanoma; Cytotoxicity; Activation; Cellular immunity; Lymphokine; Tumor cell; Granulocyte macrophage colony stimulating activity; Gamma interferon; Macrophage
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.3083507

Monocytes are a subpopulation of peripheral blood leukocytes, which when appropriately activated by the regulatory hormones of the immune system, are capable of becoming macrophages--potent effector cells for immune response to tumors and parasites. A complementary DNA for the T lymphocyte--derived lymphokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), has been cloned, and recombinant GM-CSF protein has been expressed in yeast and purified to homogeneity. This purified human recombinant GM-CSF stimulated peripheral blood monocytes in vitro to become cytotoxic for the malignant melanoma cell line A375. Another T cell--derived lymphokine, γ-interferon (IFN-γ), also stimulated peripheral blood monocytes to become tumoricidal against this malignant cell line. When IFN-γ activates monocytes to become tumoricidal, additional stimulation by exogenously added lipopolysaccharide is required. No such exogenous signals were required for the activation of monocytes by GM-CSF.