The action of bryostatin on normal human hematopoietic progenitors is mediated by accessory cell release of growth factors
| Autor: | S J, Sharkis, R J, Jones, M L, Bellis, G D, Demetri, J D, Griffin, C, Civin, W S, May |
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| Rok vydání: | 1990 |
| Předmět: |
Immunology
Antigen-Presenting Cells Granulocyte-Macrophage Colony-Stimulating Factor Antineoplastic Agents Cell Biology Hematology Blotting Northern Bryostatins Hematopoietic Cell Growth Factors Hematopoietic Stem Cells Biochemistry Antibodies Hematopoiesis Lactones Colony-Stimulating Factors Humans Interleukin-3 Macrolides RNA Messenger Growth Substances Cell Division |
| Zdroj: | Blood. 76:716-720 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v76.4.716.bloodjournal764716 |
| Popis: | Since enrichment of human bone-marrow hematopoietic progenitors is becoming more feasible and since purified growth factors are now available, we sought to study the action of growth factors on CD34- positive enriched cultures of human bone-marrow cells. We tested the effect of recombinant human (rh) granulocyte-macrophage colony- stimulating factor (GM-CSF), rh interleukin-3 (IL-3), or a unique biologic response modifier, bryostatin 1, on the growth of purified CD34 cells obtained by limiting dilution in single-cell cultures. We have shown previously that bryostatin 1 stimulates both myeloid and erythroid progenitors of human origin in vitro. In this study both IL-3 and GM-CSF supported colony formation from 500, 100, or single-cell cultures at equivalent plating efficiences, suggesting a direct action of these factors on hematopoietic cell growth. Conversely, bryostatin 1 did not support the growth of CD34 cells in single-cell cultures, and the cloning efficiency increased with increasing the number of cells in the culture. To test whether the indirect action of bryostatin 1 might be mediated through the production of growth factors by accessory cells, studies were performed using antibodies directed against human IL-3 and GM-CSF in culture with bryostatin 1 and normal human bone- marrow cells. Results are consistent with the hypothesis that bryostatin 1 could have a stimulatory effect on the accessory cell populations to produce either IL-3 or GM-CSF. Further support for this notion was obtained by demonstrating that T cells, which are cells known to be able to produce IL-3 and GM-CSF, are stimulated by bryostatin 1 to express messenger RNA (mRNA) for specific growth factors, including GM-CSF. These results provide further support that bryostatin 1 may be a useful clinical agent to stimulate hematopoiesis in vivo. |
| Databáze: | OpenAIRE |
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