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Stem cell factor (c-kit ligand) enhances the interleukin-9-dependent proliferation of human CD34+ and CD34+CD33-DR- cells.
Exp Hematol. 1994 Aug; 22(9):919-23.EH

Abstract

We have studied the effects of recombinant human interleukin-9 (IL-9), alone and combined with stem cell factor (SCF, c-kit ligand), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the clonogenic proliferation of highly enriched human hematopoietic CD34+ and CD34+CD33-DR- progenitor cells. Colony assays were performed under serum-containing and serum-free conditions. IL-9, as a single agent, did not support colony formation. The addition of erythropoietin (Epo) to IL-9 induced the growth of erythroid progenitors (BFU-E) derived from both CD34+ and CD34+CD33-DR- cells. The IL-9-dependent growth of BFU-E derived from CD34+ cells was increased in an additive manner by SCF and, to a lesser extent, by IL-3, whereas CD34+CD33-DR- erythroid precursors were also responsive to GM-CSF in combination with IL-9. The addition of SCF to IL-9 did stimulate the development of CD34+ and CD34+CD33-DR- macroscopic, multicentered BFU-E and multilineage colonies (CFU-GEMM). When IL-9 was used in serum-free conditions, the growth of CD34+ and CD34+CD33-DR- BFU-E was observed in the presence of Epo. Moreover, a marked synergy on BFU-E colony formation was evident when IL-9 was combined with SCF, and their activity was enhanced by the addition of IL-3. IL-9 showed a negligible proliferative activity on colony-forming units-granulocyte/macrophage (CFU-GM). However, it increased the number of CD34+CD33-DR- CFU-GM responsive to IL-3 (37% of the colonies generated by phytohemagglutinin-stimulated lymphocyte conditioned medium [PHA-LCM]). The effects of IL-9 on CD34+CD33-DR- cells were also studied in a short-term suspension culture system, which evaluates the proliferation of progenitors earlier than day 14 CFU-C (Delta assay). In this system, IL-9 had a minimal activity on its own. In combination with SCF, however, it induced a nine-fold expansion of CD34+CD33-DR- cells, which generated a greater number of CFU-GM than BFU-E in secondary methylcellulose cultures. These experiments indicate that IL-9 induces the proliferation of very primitive human erythroid cells, and this effect is potentiated by SCF and other cytokines. Furthermore, IL-9 synergizes in vitro with the c-kit ligand in expanding the pool of early pluripotent hematopoietic progenitor cells.

Authors+Show Affiliations

Istituto di Ematologia Seràgnoli, Università di Bologna, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7520394

Citation

Lemoli, R M., et al. "Stem Cell Factor (c-kit Ligand) Enhances the Interleukin-9-dependent Proliferation of Human CD34+ and CD34+CD33-DR- Cells." Experimental Hematology, vol. 22, no. 9, 1994, pp. 919-23.
Lemoli RM, Fortuna A, Fogli M, et al. Stem cell factor (c-kit ligand) enhances the interleukin-9-dependent proliferation of human CD34+ and CD34+CD33-DR- cells. Exp Hematol. 1994;22(9):919-23.
Lemoli, R. M., Fortuna, A., Fogli, M., Motta, M. R., Rizzi, S., Benini, C., & Tura, S. (1994). Stem cell factor (c-kit ligand) enhances the interleukin-9-dependent proliferation of human CD34+ and CD34+CD33-DR- cells. Experimental Hematology, 22(9), 919-23.
Lemoli RM, et al. Stem Cell Factor (c-kit Ligand) Enhances the Interleukin-9-dependent Proliferation of Human CD34+ and CD34+CD33-DR- Cells. Exp Hematol. 1994;22(9):919-23. PubMed PMID: 7520394.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stem cell factor (c-kit ligand) enhances the interleukin-9-dependent proliferation of human CD34+ and CD34+CD33-DR- cells. AU - Lemoli,R M, AU - Fortuna,A, AU - Fogli,M, AU - Motta,M R, AU - Rizzi,S, AU - Benini,C, AU - Tura,S, PY - 1994/8/1/pubmed PY - 1994/8/1/medline PY - 1994/8/1/entrez SP - 919 EP - 23 JF - Experimental hematology JO - Exp Hematol VL - 22 IS - 9 N2 - We have studied the effects of recombinant human interleukin-9 (IL-9), alone and combined with stem cell factor (SCF, c-kit ligand), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the clonogenic proliferation of highly enriched human hematopoietic CD34+ and CD34+CD33-DR- progenitor cells. Colony assays were performed under serum-containing and serum-free conditions. IL-9, as a single agent, did not support colony formation. The addition of erythropoietin (Epo) to IL-9 induced the growth of erythroid progenitors (BFU-E) derived from both CD34+ and CD34+CD33-DR- cells. The IL-9-dependent growth of BFU-E derived from CD34+ cells was increased in an additive manner by SCF and, to a lesser extent, by IL-3, whereas CD34+CD33-DR- erythroid precursors were also responsive to GM-CSF in combination with IL-9. The addition of SCF to IL-9 did stimulate the development of CD34+ and CD34+CD33-DR- macroscopic, multicentered BFU-E and multilineage colonies (CFU-GEMM). When IL-9 was used in serum-free conditions, the growth of CD34+ and CD34+CD33-DR- BFU-E was observed in the presence of Epo. Moreover, a marked synergy on BFU-E colony formation was evident when IL-9 was combined with SCF, and their activity was enhanced by the addition of IL-3. IL-9 showed a negligible proliferative activity on colony-forming units-granulocyte/macrophage (CFU-GM). However, it increased the number of CD34+CD33-DR- CFU-GM responsive to IL-3 (37% of the colonies generated by phytohemagglutinin-stimulated lymphocyte conditioned medium [PHA-LCM]). The effects of IL-9 on CD34+CD33-DR- cells were also studied in a short-term suspension culture system, which evaluates the proliferation of progenitors earlier than day 14 CFU-C (Delta assay). In this system, IL-9 had a minimal activity on its own. In combination with SCF, however, it induced a nine-fold expansion of CD34+CD33-DR- cells, which generated a greater number of CFU-GM than BFU-E in secondary methylcellulose cultures. These experiments indicate that IL-9 induces the proliferation of very primitive human erythroid cells, and this effect is potentiated by SCF and other cytokines. Furthermore, IL-9 synergizes in vitro with the c-kit ligand in expanding the pool of early pluripotent hematopoietic progenitor cells. SN - 0301-472X UR - https://www.unboundmedicine.com/medline/citation/7520394/Stem_cell_factor__c_kit_ligand__enhances_the_interleukin_9_dependent_proliferation_of_human_CD34+_and_CD34+CD33_DR__cells_ L2 - https://medlineplus.gov/stemcells.html DB - PRIME DP - Unbound Medicine ER -