Human interleukin-4 enhances stromal cell-dependent hematopoiesis: costimulation with stem cell factor.
Interleukin-4 (IL-4) has distinct hematopoietic activities, primarily as a costimulant with other cytokines to enhance colony formation of hematopoietic progenitors. We investigated the influence of IL-4 on stromal cell-supported long-term cultures (LTCs) of normal human bone marrow. Addition of IL-4 to LTCs of unseparated bone marrow or highly enriched CD34+ cells resulted in a significant increase of myeloid progenitors in the nonadherent, as well as in the stromal cell-adherent cell populations. In contrast, the total cell number was not influenced by IL-4, suggesting a selective effect on primitive progenitor cells. Cord blood cells or CD34+ bone marrow cells were incubated with stem cell factor (SCF) and/or IL-4 in stromal cell-free cultures. In these experiments, a twofold to fivefold increase of myeloid progenitor cells was observed in the presence of SCF and IL-4 as compared with SCF alone. Preincubation of the stromal cell cultures with IL-4 resulted in an enhanced adherence of CD34+ cells to the stromal layer. Secretion of hematopoietic growth factors produced by the stromal cells, such as granulocyte-macrophage colony-stimulating factor (G-CSF), and IL-1, was inhibited by IL-4. Thus, the increase of hematopoietic progenitors in LTCs, as observed in the presence of IL-4, can be at least partially explained by a costimulation of SCF and IL-4 on primitive progenitor cells and by an enhancement of hematopoietic cells to stroma. The downregulation of CSFs by IL-4 might prevent the expansion of the mature hematopoietic cell compartment.
Keller
U
U
Department of Medicine, Johannes-Gutenberg-University School of Medicine, Mainz, Germany.
Aman
M J
MJ
Derigs
G
G
Huber
C
C
Peschel
C
C
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000187:drug effects; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000378:metabolism; D004357:Drug Synergism; D006410:Hematopoiesis / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000008:administration & dosage*; D019089:Stem Cell Factor
D015703:Antigens, CD; D018952:Antigens, CD34; D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D019089:Stem Cell Factor; D015847:Interleukin-4