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Typus
BauernOpfer
Bearbeiter
Graf Isolan
Gesichtet
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Untersuchte Arbeit:
Seite: 13, Zeilen: 1-6, 8-34
Quelle: Demetri and Griffin 1991
Seite(n): 2791-2792, Zeilen: 2791:left col. 29-32.34-37.39-43 - right col. 1-2.4-29.33-36 - 2791:left col. 1-2.26-30.32-35
[Before the purification of individual factors, early sources of CSA] included media that was conditioned by stimulated cultures of normal blood or certain tumour cells. It was initially unclear whether these complex mixtures contained both individual factors specific for proliferation and/or separate factors that would specifically induce differentiation. Further investigation showed that many of these biological activities were attributable to the simultaneous presence of multiple factors in the crude medium. [In 1978, Byrne et al.4 reported that medium that was conditioned by mouse heart tissue was found to contain CSFs which produce in vitro colonies of granulocytes and/or macrophages.] Purification of these CSFs proved difficult and for many factors, expression, cloning and production of recombinant proteins were required to completely define the unique biological properties of individual CSFs. G-CSF was probably first identified as having a distinct activity by Burgess and Metcalf5, not by its ability to stimulate proliferation, but rather by the capacity of postendotoxin-treated mouse serum to induce differentiation in a murine leukemic cell line. Therefore, Metcalf initially termed G-CSF a granulocyte-macrophage differentiation factor (GM-DF) and he noted it to be related to (or being the same as) the so-called macrophage- and granulocyte-inducing proteins, reported by Lotem et al.6. GM-DF was shown to be separate from GM-CSF, which had been partially purified in the late 1970s. This distinction was experimentally determined by the generation of neutralizing antiserum that could block the effects of GM-CSF, but which failed to block the activity of GM-DF. GM-DF was then shown to co-purify with a novel medium that selectively stimulated the formation of granulocytic colonies from normal hematopoietic progenitor cells in vitro7 and, after further purification, this factor was ultimately renamed G-CSF8. Nicola et al.8 described the biochemical characteristics of murine G-CSF in 1983, as a hydrophobic glycoprotein with an apparent molecular weight of 24-25 Kd, containing a neuraminic acid moiety and at least one internal disulfide bond that was necessary for its biological activity. After the identification of the murine G-CSF, a human molecule with analogous activities was discovered9. Both the proliferation- and differentiation-inducing activities of the murine and human G-CSF molecules cross species boundaries, in contrast to other hematopoietic growth factors such as GM-CSF or interleukin-3 (IL-3) which are active in a species-specific manner on the neutrophilic cell lineage3. In 1986, Nomura et al.10 finally described G-CSF as a molecule that specifically induces growth of the neutrophilic granulocyte lineage of cells.

Further understanding of the biological and biochemical properties of G-CSF was greatly facilitated by cloning of the gene encoding G-CSF and the production of [recombinant protein for study11, 12.]


3. Demetri GD, Griffin JD. Granulocyte colony-stimulating factor and its receptor. Blood. 1991;78:2791-2808.

4. Byrne PV, Heit W, Kubanek B. Stimulation of in vitro granulocyte--macrophage colony formation by mouse heart conditioned medium. Br J Haematol. 1978;40:197-204.

5. Burgess AW, Metcalf D. Characterization of a serum factor stimulating the differentiation of myelomonocytic leukemic cells. Int J Cancer. 1980;26:647-654.

6. Lotem J, Lipton JH, Sachs L. Separation of different molecular forms of macrophage- and granulocyte-inducing proteins for normal and leukemic myeloid cells. Int J Cancer. 1980;25:763-771.

7. Metcalf D. Clonal extinction of myelomonocytic leukemic cells by serum from mice injected with endotoxin. Int J Cancer. 1980;25:225-233.

8. Nicola NA, Metcalf D, Matsumoto M, Johnson GR. Purification of a factor inducing differentiation in murine myelomonocytic leukemia cells. Identification as granulocyte colony-stimulating factor. J Biol Chem. 1983;258:9017-9023.

9. Nicola NA, Begley CG, Metcalf D. Identification of the human analogue of a regulator that induces differentiation in murine leukaemic cells. Nature. 1985;314:625-628.

10. Nomura H, Imazeki I, Oheda M, Kubota N, Tamura M, Ono M, Ueyama Y, Asano S. Purification and characterization of human granulocyte colonystimulating factor (G-CSF). Embo J. 1986;5:871-876.

11. Nagata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H, Ono M. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature. 1986;319:415-418.

12. Souza LM, Boone TC, Gabrilove J, Lai PH, Zsebo KM, Murdock DC, Chazin VR, Bruszewski J, Lu H, Chen KK, et al. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science. 1986;232:61-65.

[Page 2791]

Before the purification of individual factors, early sources of CSA included media conditioned by culture with stimulated normal blood or splenic leukocytes, placenta, or certain tumor cells1-5. [...] It was initially unclear whether the complex mixtures termed CSA contained individual factors specific for proliferation and separate factors that specifically induced differentiation. [...] Further investigation showed that many of these biologic activities were attributable to the simultaneous presence of multiple factors in the crude CSA. Purification of the CSFs proved difficult, and, for many factors, expression cloning and production of recombinant protein were required to completely define the unique biologic properties of individual CSFs.

[...] G-CSF was probably first identified as a distinct activity by Burgess and Metcalf, not by its ability to stimulate proliferation, but rather by the capacity of postendotoxin-treated mouse serum or conditioned media to induce differentiation of a murine myelomonocytic leukemia cell line, the differentiation-responsive (D+) subline of WEHI3B cells6,7. Therefore, G-CSF was initiaIly termed a granulocyte-macrophage differentiation factor (GM-DF) by Metcalf’ and was noted to be related to (or the same as) a differentiating activity named MGI-1G by Lotem et al.8 G-CSF was shown to be separate from GM-CSF, which had been partially purified in the late 1970s. This distinction was experimentally determined by the generation of neutralizing antisera that could block the effects of GM-CSF but which failed to block the activity of GM-DF. GM-DF was then shown to copurify with a novel activity that selectively stimulated the formation of granulocytic colonies by normal hematopoietic progenitor cells in vitro,’ and after further purification, this factor was ultimately renamed G-CSF.9 Nicola et al9 described the biochemical characteristics of murine G-CSF in 1983 as a hydrophobic glycoprotein with an apparent molecular weight of 24 or 25 Kd, containing a neuraminic acid moiety and at least one internal disulfide bond necessary for biologic activity.

After the identification of the murine G-CSF, a human molecule with analogous activities was discovered. [...] Both the proliferation- and differentiation-inducing activities of the murine and human G-CSF molecules crossed species boundaries, in contrast to other hematopoietic growth factors such as

[Page 2792]

GM-CSF or interleukin-3 (IL-3), which are active on the neutrophilic lineage in a species-specific manner. [...] Nomura et al15 purified native human G-CSF from culture medium conditioned by the tumor cell line CHU-2 and described its properties as a molecule that specifically induced the growth of cells of the neutrophilic granulocyte lineage.15

CLONING OF THE G-CSF GENE

Further understanding of the biologic and biochemical properties of G-CSF was greatly facilitated by cloning of the gene encoding G-CSF and the production of recombinant protein for study.


1. Metcalf D: The granulocyte-macrophage colony-stimulating factors. Science 229:16, 1985

2. Metcalf D: The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells. Nature 339:27, 1989

3. Sachs L The molecular control of blood cell development. Science 238:1374, 1987

4. Quesenberry P, Levitt L Hematopoietic stem cells. N Engl J Med 301:755,1979

5. Golde D, Cline M: Regulation of granulopoiesis. N Engl J Med 291:1388,1974

6. Burgess A, Metcalf D: Characterization of a serum factor stimulating the differentiation of myelomonocytic leukemia cells. Int J Cancer 26:647,1980

7. Metcalf D: Clonal extinction of myelomonocytic leukemia cells by serum from mice injected with endotoxin. Int J Cancer 25:225,1980

8. Lotem J, Lipton J, Sachs L Separation of different molecular forms of macrophage and granulocyte-inducing proteins for normal and leukemic myeloid cells. Int J Cancer 25:763,1980

9. Nicola NA, Metcalf D, Matsumoto M, Johnson G R Purification of a factor inducing differentiation in murine myelomonocytic leukemia cells. Identification as granulocyte colony-stimulating factor. J Biol Chem 258:9017,1983

10. Nicola NA, Begley CG, Metcalf D: Identification of the human analogue of a regulator that induces differentiation in murine leukaemic cells. Nature 314:625,1985

14. Souza LM, Boone TC, Gabrilove J, Lai PH, Zsebo KM, Murdock DC, Chazin VR, Bruszewski J, Lu H, Chen KK, Barendt J, Platzer E, Moore MAS, Mertelsmann R, Welte K Recombinant human granulocyte colony-stimulating factor: Effects on normal and leukemic myeloid cells. Science 232:61,1986

15. Nomura H, Imazeki I, Oheda M, Kubota N, Tamura M, Ono M, Ueyama Y, Asano S: Purification and characterization of human granulocyte colony-stimulating actor (G-CSF). EMBO J 5:871,1986

17. Nagata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto 0, Hirata Y, Kubota N, Oheda M, Nomura H, Ono M: Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 319:415,1986

Anmerkungen

Although in this page all but one sentence has been taken - mostly verbatim - from the source Demetri and Griffin (1991) nothing has been marked as a citation, and the source is only given in passing.

Sichter
(Graf Isolan) Agrippina1

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