Interleukin-11 stimulates the proliferation of human hematopoietic CD34+ and CD34+CD33-DR-cells and synergizes with stem cell factor, interleukin-3, and granulocyte-macrophage colony-stimulating factor

R. M. Lemoli, M. Fogli, A. Fortuna, M. R. Motta, S. Rizzi, C. Benini, S. Tura

Research output: Contribution to journalArticle

Abstract

We have studied the effects of recombinant human interleukin-11 rhIL-11), alone and combined with stem cell factor (SCF or c-kit ligand), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the proliferation of highly enriched human hematopoietic CD34+ and CD34+CD33-DR- progenitor cells. CD34+ cells were purified using the avidin-biotin immunoabsorption technique and CD33+DR+ cells were subsequently removed by immunomagnetic separation. The colony assays were performed in the presence and absence of exogenous serum. IL-11, as a single agent, induced the growth of a small number of colony-forming units-granulocyte/macrophage (CFU-GM) derived from purified CD34+ cells and failed to support the colony growth of CD34+CD33-DR- cells. The addition of erythropoietin (Epo) to LL-11 induced the growth of erythroid progenitors (BFU-E) derived from CD34+ cells but not from the same population depleted of CD33+DR+ cells. The combination of IL-11 1 with SCF, IL-3, or GM-CSF, in the presence of Epo, resulted in a synergistic or additive increase in the number of CFU cells (CFU-C) derived from both cell fractions. Moreover, the addition of SCF to IL-11 stimulated the development of macroscopic erythroid and multilineage colonies (cFu-GEMM) containing more than 104 cells. A combination of three factors (IL-11, SCF, and IL-3) resulted in the increase of the number of colonies arising from CD34+ and CD34+CD33-DR- cells (but not of their size) compared to the cultures treated with IL-11 1 plus SCF or IL-11 1 plus IL-3. The pattern of proliferative response of primitive hematopoietic progenitor cells to IL-11 in serum-free conditions was very similar to the cultures grown in serum-containing medium. It is noteworthy that IL-11 and SCF yielded colony formation that was comparable to that observed in the presence of serum. The effects of IL-11 on CD34+CD33-DR- cells were also studied in a short-term suspension culture system, which was shown to be specific for evaluating the proliferation of pluripotent hematopoietic precursors (Delta assay). In this system, IL-11 had a minimal effect on its own, whereas IL-11 plus SCF acted synergistically and their proliferative activity was improved by the addition of GM-CSF. These experiments indicate that IL-11 may be considered a 'permissive' cytokine, capable of initiating the proliferation of very primitive human hematopoietic cells, which are then able to respond to late-acting CSFs. Also, IL-11 1 synergizes in vitro with SCF in expanding the pool of early hematopoietic progenitor cells.

Original languageEnglish
Pages (from-to)1668-1672
Number of pages5
JournalExperimental Hematology
Volume21
Issue number13
Publication statusPublished - 1993

Fingerprint

Interleukin-11
Stem Cell Factor
Interleukin-3
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-1
oprelvekin
Erythropoietin
Hematopoietic Stem Cells
Serum
Growth
Immunomagnetic Separation
Granulocyte-Macrophage Progenitor Cells
Erythroid Precursor Cells
Avidin
Biotin

Keywords

  • Cytokines
  • Hematopoietic cells
  • IL-11
  • Proliferation
  • Synergism

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Interleukin-11 stimulates the proliferation of human hematopoietic CD34+ and CD34+CD33-DR-cells and synergizes with stem cell factor, interleukin-3, and granulocyte-macrophage colony-stimulating factor. / Lemoli, R. M.; Fogli, M.; Fortuna, A.; Motta, M. R.; Rizzi, S.; Benini, C.; Tura, S.

In: Experimental Hematology, Vol. 21, No. 13, 1993, p. 1668-1672.

Research output: Contribution to journalArticle

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T1 - Interleukin-11 stimulates the proliferation of human hematopoietic CD34+ and CD34+CD33-DR-cells and synergizes with stem cell factor, interleukin-3, and granulocyte-macrophage colony-stimulating factor

AU - Lemoli, R. M.

AU - Fogli, M.

AU - Fortuna, A.

AU - Motta, M. R.

AU - Rizzi, S.

AU - Benini, C.

AU - Tura, S.

PY - 1993

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N2 - We have studied the effects of recombinant human interleukin-11 rhIL-11), alone and combined with stem cell factor (SCF or c-kit ligand), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the proliferation of highly enriched human hematopoietic CD34+ and CD34+CD33-DR- progenitor cells. CD34+ cells were purified using the avidin-biotin immunoabsorption technique and CD33+DR+ cells were subsequently removed by immunomagnetic separation. The colony assays were performed in the presence and absence of exogenous serum. IL-11, as a single agent, induced the growth of a small number of colony-forming units-granulocyte/macrophage (CFU-GM) derived from purified CD34+ cells and failed to support the colony growth of CD34+CD33-DR- cells. The addition of erythropoietin (Epo) to LL-11 induced the growth of erythroid progenitors (BFU-E) derived from CD34+ cells but not from the same population depleted of CD33+DR+ cells. The combination of IL-11 1 with SCF, IL-3, or GM-CSF, in the presence of Epo, resulted in a synergistic or additive increase in the number of CFU cells (CFU-C) derived from both cell fractions. Moreover, the addition of SCF to IL-11 stimulated the development of macroscopic erythroid and multilineage colonies (cFu-GEMM) containing more than 104 cells. A combination of three factors (IL-11, SCF, and IL-3) resulted in the increase of the number of colonies arising from CD34+ and CD34+CD33-DR- cells (but not of their size) compared to the cultures treated with IL-11 1 plus SCF or IL-11 1 plus IL-3. The pattern of proliferative response of primitive hematopoietic progenitor cells to IL-11 in serum-free conditions was very similar to the cultures grown in serum-containing medium. It is noteworthy that IL-11 and SCF yielded colony formation that was comparable to that observed in the presence of serum. The effects of IL-11 on CD34+CD33-DR- cells were also studied in a short-term suspension culture system, which was shown to be specific for evaluating the proliferation of pluripotent hematopoietic precursors (Delta assay). In this system, IL-11 had a minimal effect on its own, whereas IL-11 plus SCF acted synergistically and their proliferative activity was improved by the addition of GM-CSF. These experiments indicate that IL-11 may be considered a 'permissive' cytokine, capable of initiating the proliferation of very primitive human hematopoietic cells, which are then able to respond to late-acting CSFs. Also, IL-11 1 synergizes in vitro with SCF in expanding the pool of early hematopoietic progenitor cells.

AB - We have studied the effects of recombinant human interleukin-11 rhIL-11), alone and combined with stem cell factor (SCF or c-kit ligand), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the proliferation of highly enriched human hematopoietic CD34+ and CD34+CD33-DR- progenitor cells. CD34+ cells were purified using the avidin-biotin immunoabsorption technique and CD33+DR+ cells were subsequently removed by immunomagnetic separation. The colony assays were performed in the presence and absence of exogenous serum. IL-11, as a single agent, induced the growth of a small number of colony-forming units-granulocyte/macrophage (CFU-GM) derived from purified CD34+ cells and failed to support the colony growth of CD34+CD33-DR- cells. The addition of erythropoietin (Epo) to LL-11 induced the growth of erythroid progenitors (BFU-E) derived from CD34+ cells but not from the same population depleted of CD33+DR+ cells. The combination of IL-11 1 with SCF, IL-3, or GM-CSF, in the presence of Epo, resulted in a synergistic or additive increase in the number of CFU cells (CFU-C) derived from both cell fractions. Moreover, the addition of SCF to IL-11 stimulated the development of macroscopic erythroid and multilineage colonies (cFu-GEMM) containing more than 104 cells. A combination of three factors (IL-11, SCF, and IL-3) resulted in the increase of the number of colonies arising from CD34+ and CD34+CD33-DR- cells (but not of their size) compared to the cultures treated with IL-11 1 plus SCF or IL-11 1 plus IL-3. The pattern of proliferative response of primitive hematopoietic progenitor cells to IL-11 in serum-free conditions was very similar to the cultures grown in serum-containing medium. It is noteworthy that IL-11 and SCF yielded colony formation that was comparable to that observed in the presence of serum. The effects of IL-11 on CD34+CD33-DR- cells were also studied in a short-term suspension culture system, which was shown to be specific for evaluating the proliferation of pluripotent hematopoietic precursors (Delta assay). In this system, IL-11 had a minimal effect on its own, whereas IL-11 plus SCF acted synergistically and their proliferative activity was improved by the addition of GM-CSF. These experiments indicate that IL-11 may be considered a 'permissive' cytokine, capable of initiating the proliferation of very primitive human hematopoietic cells, which are then able to respond to late-acting CSFs. Also, IL-11 1 synergizes in vitro with SCF in expanding the pool of early hematopoietic progenitor cells.

KW - Cytokines

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KW - IL-11

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