Introduction of the human interleukin-6 (IL-6) receptor in murine IL-3-
dependent hematopoietic cells restores responsiveness to IL-6
I Touw, R van Gurp, P Schipper, T van Agthoven and B Lowenberg
Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
To create experimental systems that facilitate studies aimed at the
responsiveness of hematopoietic progenitors to interleukin (IL)-6 in
combination with IL-3, we introduced the human IL-6 receptor (hIL-6R) into
the IL-3-dependent cell line 32D. For this purpose, a retroviral vector
containing the hIL-6R cDNA was constructed. 32D parental cells did not
respond to IL-6, neither alone nor in combination with increasing
concentrations of IL-3, and did not express detectable numbers of IL-6R as
determined by 125I-IL-6 binding. 32D/hIL-6R cells expressed high-affinity
IL-6 binding and responded synergistically to IL-6 in combination with
suboptimal amounts of IL-3 in DNA synthesis assays. In addition, IL-6
promoted the short-term survival of IL-3- responsive clonogenic 32D/hIL-6R
cells. On the other hand, although introduction of hIL-6R resulted in the
formation of high-affinity IL-6 receptor structures in the IL-2-dependent
thymocyte cell line CTLL, CTLL/hIL-6R cells did not respond to IL-6 in
synergy with IL-2. We conclude that 32D cells possess the intracellular
machinery permissive for IL-6 signal transduction. Murine IL-3-dependent
cell lines with ectopic IL-6 receptors can serve as models for dissecting
the molecular basis of IL-6 responses in primitive hematopoietic cells.
Volume 79,
Issue 11,
pp. 2867-2872,
06/01/1992
Copyright © 1992 by The American Society of Hematology
