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.
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 immuno-magnetic 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 IL-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 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 10(4) 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 plus SCF or IL-11 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.(ABSTRACT TRUNCATED AT 400 WORDS)
Lemoli
R M
RM
Istituto di Ematologia Seràgnoli, Università di Bologna, Italy.
Fogli
M
M
Fortuna
A
A
Motta
M R
MR
Rizzi
S
S
Benini
C
C
Tura
S
S
D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis*; D001769:Blood; D001854:Bone Marrow Cells; D002455:Cell Division; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000032:analysis*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D063268:Sialic Acid Binding Ig-like Lectin 3; D019089:Stem Cell Factor
D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D006684:HLA-DR Antigens; D016298:Hematopoietic Cell Growth Factors; D017370:Interleukin-11; D007377:Interleukin-3; D011994:Recombinant Proteins; D063268:Sialic Acid Binding Ig-like Lectin 3; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor