Stem Cells, Vol 12, 638-649, Copyright © 1994 by AlphaMed Press
Interleukin 4 alters human bone marrow stroma and modulates its interaction with hematopoietic progenitors
A Ferrajoli, M Talpaz, NG Ordonez, ER Stanley, C Hirsch-Ginsberg, TF Zipf, M Wetzler, R Kurzrock and Z Estrov
Department of Clinical Investigation, University of Texas M.D. Anderson Cancer Center, Houston 77030.
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.
