Human granulocyte colony-stimulating factor: Biologic activities and receptor characterization on hematopoietic cells and small cell lung cancer cell lines

B. R. Avalos, J. C. Gasson, C. Hedvat, S. G. Quan, G. C. Baldwin, R. H. Weisbart, R. E. Williams, D. W. Golde, J. F. DiPersio

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224 Scopus citations

Abstract

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 cytotoxicity (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 125I-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.

Original languageEnglish
Pages (from-to)851-857
Number of pages7
JournalBlood
Volume75
Issue number4
DOIs
StatePublished - 1990

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