Human granulocyte colony-stimulating factor: biologic activities and receptor characterization on hematopoietic cells and small cell lung cancer cell lines.
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 125l-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.
Avalos
B R
BR
Department of Internal Medicine, Ohio State University, Columbus 43210.
Gasson
J C
JC
Hedvat
C
C
Quan
S G
SG
Baldwin
G C
GC
Weisbart
R H
RH
Williams
R E
RE
Golde
D W
DW
DiPersio
J F
JF
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D001095:Arachidonic Acids / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D001854:Bone Marrow Cells; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000378:metabolism* / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006413:Hematopoietic System / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D001095:Arachidonic Acids; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D013481:Superoxides; D016179:Granulocyte Colony-Stimulating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor