Human Granulocyte Colony-Stimulating Factor: Biologic Activities and Receptor Characterization on Hematopoietic Cells and Small Cell Lung Cancer Cell Lines

• Published in: Blood 1990-02, Vol.75 (4), p.851-857
• Main Authors: Avalos, Belinda R., Gasson, Judith C., Hedvat, Cyrus, Quan, Shirley G., Baldwin, Gayle C., Weisbart, Richard H., Williams, Robert E., Golde, David W., DiPersio, John F.
• Format: Article
• Language: English
• Subjects: Antibody-Dependent Cell Cytotoxicity - drug effects; Arachidonic Acids - metabolism; Biological and medical sciences; Bone Marrow - drug effects; Bone Marrow - metabolism; Bone Marrow Cells; Carcinoma, Small Cell - metabolism; Carcinoma, Small Cell - pathology; Carcinoma, Small Cell - ultrastructure; Cell Division - drug effects; Cell Line; Colony-Stimulating Factors - metabolism; Colony-Stimulating Factors - pharmacology; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances - pharmacology; Hematologic and hematopoietic diseases; Hematopoietic System - cytology; Hematopoietic System - metabolism; Hematopoietic System - ultrastructure; Humans; Iodine Radioisotopes - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - ultrastructure; Medical sciences; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophils - drug effects; Neutrophils - metabolism; Receptors, Cell Surface - analysis; Receptors, Cell Surface - drug effects; Receptors, Cell Surface - metabolism; Receptors, Granulocyte Colony-Stimulating Factor; Recombinant Proteins - metabolism; Superoxides - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V75.4.851.851

Human granulocyte colony-stimulating factor (G-CSF) is a regulatory glycoprotein that stimulates the production of neutrophilic granulocytes from committed hematopoietic progenitor cells both in vitro and in vivo. In this report, we show that biosynthetic (recombinant) human G-CSF enhances colony formation by normal human bone marrow and the human myeloid leukemic cell lines, HL-60 and KG-1, as well as nonhematopoietic small cell lung cancer lines, H128 and H69. G-CSF also modulates multiple differentiated functions of human neutrophils, including enhanced oxidative metabolism in response to f-Met-Leu-Phe (f-MLP), increased antibody-dependent cell-mediated cytoxicity (ADCC), and augmented arachidonic acid release in response to ionophore and chemotactic agents. These effects are all maximal at a concentration of 100 to 500 pmol/L. Using 126l-labeled recombinant human G-CSF, high affinity binding sites were identified on human neutrophils, the myeloid leukemia cell lines KG-1 and HL-60, and the small cell carcinoma cell lines, H128 and H69. G-CSF receptor numbers ranged between 138 and 285 sites per cell with a kd of 77 to 140 pmol/L, consistent with the concentrations of G-CSF that elicit biologic responses in vitro. Decreased specific binding of 125I-G-CSF by human neutrophils was consistently observed in the presence of excess unlabeled human granulocyte-macrophage colony-stimulating factor (GM-CSF), suggesting competition or down modulation by GM-CSF of the G-CSF receptor.