Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Jul;82(1):255–261. doi: 10.1172/JCI113579

Hemopoietic colony growth-promoting activities in the plasma of bone marrow transplant recipients.

K Yamasaki 1, L A Solberg Jr 1, N Jamal 1, G Lockwood 1, D Tritchler 1, J E Curtis 1, M M Minden 1, K G Mann 1, H A Messner 1
PMCID: PMC303502  PMID: 3292585

Abstract

Plasma samples were obtained from 34 bone marrow transplant (BMT) recipients before and after administration of the preparative regimen and tested for their ability to promote and/or support growth of hemopoietic colonies. The ability of plasma samples to promote colony formation on their own was tested on normal nonadherent target cells without addition of exogenous growth factors. The growth-supporting activity was examined in the presence of medium conditioned by phytohemagglutinin-stimulated leukocytes (PHA-LCM) and/or erythropoietin (EPO). A series of kinetic changes was routinely observed. Pretransplant samples rarely gave rise to colonies without addition of exogenous growth factors. Plasma samples obtained after completion of the preparative regimen demonstrated increments of growth-promoting activities for megakaryocyte and granulocyte-macrophage progenitors (CFU-Meg and CFU-GM), respectively, that peaked between 7 and 21 d after transplantation. By day 30, activity levels of some patients had returned to pretransplant values, whereas in other patients, activities remained elevated. Persisting activity levels were associated with delayed engraftment. In contrast, activities for progenitors committed to erythropoiesis (BFU-E) and pluripotent precursors (CFU-GEMM) were only rarely observed. The activities were independent of febrile episodes. Their growth-promoting influence on CFU-GM could be neutralized completely by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies. These data suggest that at least some of the observed activities in post-BMT plasma are related to GM-CSF. The growth-supporting activities of pretransplant plasma samples are lower than normal plasma when tested on CFU-Meg and CFU-GM. The growth-supporting activities improved transiently within the first month after BMT. A decline during the second and third month was followed by a gradual return to activity levels that were comparable to normal plasma. The effects of these plasma samples on BFU-E and CFU-GEMM were assessed with PHA-LCM and EPO. Similar to CFU-Meg- and CFU-GM-supporting capabilities, they improved transiently after BMT with a return of normal support function after 5-6 mo. The observed endogenous production of growth-promoting and growth-supporting activities for hemopoietic progenitors may serve as a background to design clinical trials for the timely administration of recombinant hemopoietic growth factors to BMT recipients.

Full text

PDF
255

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aye M. T., Niho Y., Till J. E., McCulloch E. A. Studies of leukemic cell populations in culture. Blood. 1974 Aug;44(2):205–219. [PubMed] [Google Scholar]
  2. Björck L., Kronvall G. Purification and some properties of streptococcal protein G, a novel IgG-binding reagent. J Immunol. 1984 Aug;133(2):969–974. [PubMed] [Google Scholar]
  3. Curtis J. E., Messner H. A. Bone marrow transplantation for leukemia and aplastic anemia: management of ABO incompatibility. Can Med Assoc J. 1982 Mar 15;126(6):649–655. [PMC free article] [PubMed] [Google Scholar]
  4. Donahue R. E., Wang E. A., Stone D. K., Kamen R., Wong G. G., Sehgal P. K., Nathan D. G., Clark S. C. Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF. 1986 Jun 26-Jul 2Nature. 321(6073):872–875. doi: 10.1038/321872a0. [DOI] [PubMed] [Google Scholar]
  5. Donahue R. E., Wang E. A., Stone D. K., Kamen R., Wong G. G., Sehgal P. K., Nathan D. G., Clark S. C. Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF. 1986 Jun 26-Jul 2Nature. 321(6073):872–875. doi: 10.1038/321872a0. [DOI] [PubMed] [Google Scholar]
  6. Emerson S. G., Sieff C. A., Wang E. A., Wong G. G., Clark S. C., Nathan D. G. Purification of fetal hematopoietic progenitors and demonstration of recombinant multipotential colony-stimulating activity. J Clin Invest. 1985 Sep;76(3):1286–1290. doi: 10.1172/JCI112087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eschbach J. W., Egrie J. C., Downing M. R., Browne J. K., Adamson J. W. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial. N Engl J Med. 1987 Jan 8;316(2):73–78. doi: 10.1056/NEJM198701083160203. [DOI] [PubMed] [Google Scholar]
  8. Glucksberg H., Storb R., Fefer A., Buckner C. D., Neiman P. E., Clift R. A., Lerner K. G., Thomas E. D. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974 Oct;18(4):295–304. doi: 10.1097/00007890-197410000-00001. [DOI] [PubMed] [Google Scholar]
  9. Groopman J. E., Mitsuyasu R. T., DeLeo M. J., Oette D. H., Golde D. W. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med. 1987 Sep 3;317(10):593–598. doi: 10.1056/NEJM198709033171003. [DOI] [PubMed] [Google Scholar]
  10. Kaspar L. V., Seed T. M. CFU-GM colony-enhancing activity in sera of dogs under acute and chronic gamma-irradiation regimens. Acta Haematol. 1984;71(3):189–197. doi: 10.1159/000206583. [DOI] [PubMed] [Google Scholar]
  11. Kaushansky K., O'Hara P. J., Berkner K., Segal G. M., Hagen F. S., Adamson J. W. Genomic cloning, characterization, and multilineage growth-promoting activity of human granulocyte-macrophage colony-stimulating factor. Proc Natl Acad Sci U S A. 1986 May;83(10):3101–3105. doi: 10.1073/pnas.83.10.3101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kawasaki E. S., Ladner M. B., Wang A. M., Van Arsdell J., Warren M. K., Coyne M. Y., Schweickart V. L., Lee M. T., Wilson K. J., Boosman A. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science. 1985 Oct 18;230(4723):291–296. doi: 10.1126/science.2996129. [DOI] [PubMed] [Google Scholar]
  13. Lee F., Yokota T., Otsuka T., Gemmell L., Larson N., Luh J., Arai K., Rennick D. Isolation of cDNA for a human granulocyte-macrophage colony-stimulating factor by functional expression in mammalian cells. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4360–4364. doi: 10.1073/pnas.82.13.4360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Li S., Champlin R., Fitchen J. H., Gale R. P. Abnormalities of myeloid progenitor cells after "successful" bone marrow transplantation. J Clin Invest. 1985 Jan;75(1):234–241. doi: 10.1172/JCI111679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lim B., Jamal N., Messner H. A. Flexible association of hemopoietic differentiation programs in multilineage colonies. J Cell Physiol. 1984 Nov;121(2):291–297. doi: 10.1002/jcp.1041210205. [DOI] [PubMed] [Google Scholar]
  16. Lin F. K., Suggs S., Lin C. H., Browne J. K., Smalling R., Egrie J. C., Chen K. K., Fox G. M., Martin F., Stabinsky Z. Cloning and expression of the human erythropoietin gene. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7580–7584. doi: 10.1073/pnas.82.22.7580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mazur E. M., de Alarcón P., South K., Miceli L. Human serum megakaryocyte colony-stimulating activity increases in response to intensive cytotoxic chemotherapy. Exp Hematol. 1984 Sep;12(8):624–628. [PubMed] [Google Scholar]
  18. Messner H. A., Curtis J. E., Minden M. D., Tritchler D., Lockwood G., Takahashi T., Lepine J., Jamal N., Tweeddale M., Wandl U. Clonogenic hemopoietic precursors in bone marrow transplantation. Blood. 1987 Nov;70(5):1425–1432. [PubMed] [Google Scholar]
  19. Messner H. A., Jamal N., Izaguirre C. The growth of large megakaryocyte colonies from human bone marrow. J Cell Physiol Suppl. 1982;1:45–51. doi: 10.1002/jcp.1041130410. [DOI] [PubMed] [Google Scholar]
  20. Messner H. A., Yamasaki K., Jamal N., Minden M. M., Yang Y. C., Wong G. G., Clark S. C. Growth of human hemopoietic colonies in response to recombinant gibbon interleukin 3: comparison with human recombinant granulocyte and granulocyte-macrophage colony-stimulating factor. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6765–6769. doi: 10.1073/pnas.84.19.6765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Messner H., Till J. E., McCulloch E. A. Density distributions of marrow cells from mouse and man. Ser Haematol. 1972;5(2):22–36. [PubMed] [Google Scholar]
  22. Miura M., Jackson C. W., Lyles S. A. Increases in circulating megakaryocyte growth-promoting activity in the plasma of rats following whole body irradiation. Blood. 1984 May;63(5):1060–1066. [PubMed] [Google Scholar]
  23. Moore M. A., Warren D. J. Synergy of interleukin 1 and granulocyte colony-stimulating factor: in vivo stimulation of stem-cell recovery and hematopoietic regeneration following 5-fluorouracil treatment of mice. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7134–7138. doi: 10.1073/pnas.84.20.7134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nagata S., Tsuchiya M., Asano S., Kaziro Y., Yamazaki T., Yamamoto O., Hirata Y., Kubota N., Oheda M., Nomura H. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. 1986 Jan 30-Feb 5Nature. 319(6052):415–418. doi: 10.1038/319415a0. [DOI] [PubMed] [Google Scholar]
  25. Nagata S., Tsuchiya M., Asano S., Kaziro Y., Yamazaki T., Yamamoto O., Hirata Y., Kubota N., Oheda M., Nomura H. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. 1986 Jan 30-Feb 5Nature. 319(6052):415–418. doi: 10.1038/319415a0. [DOI] [PubMed] [Google Scholar]
  26. Sieff C. A., Emerson S. G., Donahue R. E., Nathan D. G., Wang E. A., Wong G. G., Clark S. C. Human recombinant granulocyte-macrophage colony-stimulating factor: a multilineage hematopoietin. Science. 1985 Dec 6;230(4730):1171–1173. doi: 10.1126/science.3877981. [DOI] [PubMed] [Google Scholar]
  27. Solberg L. A., Jr, Jamal N., Messner H. A. Characterization of human megakaryocytic colony formation in human plasma. J Cell Physiol. 1985 Jul;124(1):67–74. doi: 10.1002/jcp.1041240112. [DOI] [PubMed] [Google Scholar]
  28. Souza L. M., Boone T. C., Gabrilove J., Lai P. H., Zsebo K. M., Murdock D. C., Chazin V. R., Bruszewski J., Lu H., Chen K. K. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science. 1986 Apr 4;232(4746):61–65. doi: 10.1126/science.2420009. [DOI] [PubMed] [Google Scholar]
  29. Wong G. G., Witek J. S., Temple P. A., Wilkens K. M., Leary A. C., Luxenberg D. P., Jones S. S., Brown E. L., Kay R. M., Orr E. C. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985 May 17;228(4701):810–815. doi: 10.1126/science.3923623. [DOI] [PubMed] [Google Scholar]
  30. Yang Y. C., Ciarletta A. B., Temple P. A., Chung M. P., Kovacic S., Witek-Giannotti J. S., Leary A. C., Kriz R., Donahue R. E., Wong G. G. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell. 1986 Oct 10;47(1):3–10. doi: 10.1016/0092-8674(86)90360-0. [DOI] [PubMed] [Google Scholar]
  31. de Alarcon P. A., Schmieder J. A. Megakaryocyte colony stimulating activity (Mk-CSA) in serum from patients undergoing bone marrow transplantation. Prog Clin Biol Res. 1986;215:335–340. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES