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Granulocyte colony-stimulating factor: biology and clinical potential

  • Maryann Foote
  • Bertrand C. Liang
  • Jeffrey Crawford
  • Frankie A. Holmes
  • Michael Green
  • Frankie A. Holmes
  • Michael Green
  • George Morstyn
Chapter

Abstract

The study of hematopoiesis was greatly facilitated in the mid-1960s when techniques for studying hematopoietic cells in clonal culture were developed. Initially, serum or conditioned medium was added to cultures as a source of growth factors, the colony-stimulating factors (CSFs) [58]. One of the factors that was isolated, purified, cloned, and produced in commercial quantities was granulocyte-colony stimulating factor (G-CSF), a protein that acts on the neutrophil lineage to selectively stimulate the proliferation and differentiation of committed progenitor cells and activation of mature neutrophils (Fig. 1). A property that distinguished G-CSF from other CSFs and facilitated its purification, molecular cloning, and large-scale production in prokaryotic cells was its ability to induce terminal differentiation of a murine leukemic cell line (WEHI-3B). After observing that serum from endotoxin-treated mice was capable of causing the differentiation of a WEHI-3B myelomonocytic leukemic cell line, Metcalf [57] named the activity GM—DF (granulocyte-macrophage differentiating factor). Further analysis showed that this serum contained G—CSF as well as granulocyte-macrophage colony-stimulating factor (GM-CSF). Nicola et al. [70] further purified GCSF from medium conditioned by lung tissue of endotoxin-treated mice. This G-CSF could stimulate WEHI-3B cells as well as normal cells, supporting the formation of numerous small, neutrophil-containing colonies at a concentration similar to that needed for WEHI-3B differentiation [69]. Subsequently, murine G-CSF was identified as a protein and was shown to have both differentiation-inducing activity for WEHI-3B as well as granulocyte colony-stimulating activity in bone-marrow cells [70]. Other researchers, notably Asano et al. [4] and Welte et al. [105], found several human carcinoma cells that constitutively produce colony-stimulating factors. One of these factors was purified to apparent homogeneity from the conditioned medium of bladder carcinoma 5637 cells [105] or a squamous carcinoma cell line [73]. The purified CSF selectively stimulated neutrophilic granulocyte-colony formation from bone-marrow cells, so it was concluded that this factor was the human counterpart to mouse G-CSF. The protein initially identified as G-CSF was also called CSF-13 and Pluripoietin (pCSF).

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© Springer Science+Business Media Dordrecht 2003

Authors and Affiliations

  • Maryann Foote
  • Bertrand C. Liang
  • Jeffrey Crawford
  • Frankie A. Holmes
  • Michael Green
  • Frankie A. Holmes
  • Michael Green
  • George Morstyn

There are no affiliations available

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