Interleukin 4 alters human bone marrow stroma and modulates its interaction with hematopoietic progenitors.
To investigate the functional activity of interleukin 4 (IL-4) on human marrow stroma formation, normal bone marrow (BM) samples were cultured in "Dexter-type" long-term cultures in the presence and absence of IL-4. IL-4 (0.001 to 1.0 micrograms/ml) added at the initiation of culture and once weekly when the cultures were fed effaced the culture architecture. In four-week old confluent cultures smooth muscle-like and endothelial-like cells were rare, the fibronectin network and cobblestone areas were absent, and a preponderance of monocyte-macrophages characterized the adherent layer. Exposure to IL-4 reduced the numbers of CD34+ cells, colony-forming unit granulocyte-macrophage (GFU-GM) cells and burst-forming unit-erythroid (BFU-E) cells in the adherent layer, and increased their numbers in the nonadherent layer. In five of eight IL-4-containing cultures the concentrations of macrophage colony-stimulating factor (M-CSF) were increased and in two of eight IL-4-treated cultures the concentrations of tumor necrosis factor-alpha (TNF-alpha) were significantly elevated as compared to those in control cultures, whereas there were no consistent differences in the levels of either IL-6 or transforming growth factor-beta (TGF-beta). IL-1 beta and granulocyte-macrophage CSF (GM-CSF) were not detected in any culture. These data suggest that IL-4 suppresses stroma formation and alters its structure and cellular composition.
Ferrajoli
A
A
Department of Clinical Investigation, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Talpaz
M
M
Ordonez
N G
NG
Stanley
E R
ER
Hirsch-Ginsberg
C
C
Zipf
T F
TF
Wetzler
M
M
Kurzrock
R
R
Estrov
Z
Z
D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34; D001853:Bone Marrow / Q000187:drug effects* / Q000276:immunology; D001854:Bone Marrow Cells; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015703:Antigens, CD; D018952:Antigens, CD34; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor