Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells

Autor: LM Souza, TC Boone, J Gabrilove, PH Lai, KM Zsebo, DC Murdock, VR Chazin, J Bruszewski, H Lu, KK Chen, J. Barendt, E. Platzer, M. A. S. Moore, R. Mertelsmann, K. Welte
Rok vydání: 1986
Předmět:
Zdroj: Science. 232:61-65
ISSN: 1095-9203
0036-8075
DOI: 10.1126/science.232.4746.61
Popis: Experiments were conducted to isolate and characterize the gene and gene product of a human hematopoietic colony-stimulating factor with pluripotent biological activities. This factor has the ability to induce differentiation of a murine myelomonocytic leukemia cell line WEHI-3B(D+) and cells from patients with newly diagnosed acute nonlymphocytic leukemia (ANLL). A complementary DNA copy of the gene encoding a pluripotent human granulocyte colony-stimulating factor (hG-CSF) was cloned and expressed in Escherichia coli. The recombinant form of hG-CSF is capable of supporting neutrophil proliferation in a CFU-GM assay. In addition, recombinant hG-CSF can support early erythroid colonies and mixed colony formation. Competitive binding studies done with 125I-labeled hG-CSF and cell samples from two patients with newly diagnosed human leukemias as well as WEHI-3B(D+) cells showed that one of the human leukemias (ANLL, classified as M4) and the WEHI-3B(D+) cells have receptors for hG-CSF. Furthermore, the murine WEHI-3B(D+) cells and human leukemic cells classified as M2, M3, and M4 were induced by recombinant hG-CSF to undergo terminal differentiation to macrophages and granulocytes. The secreted form of the protein produced by the bladder carcinoma cell line 5637 was found to be O-glycosylated and to have a molecular weight of 19,600.
Databáze: OpenAIRE