Further studies on growth factor production by the TC-1 stromal cell line:
pre-B stimulating activity
TA Woodward, IK McNiece, PL Witte, P Bender, R Crittenden, DS Temeles, BE Robinson, GB Baber, DH Deacon and PC Isakson
Department of Internal Medicine, University of Virginia School of Medicine,
Charlottesville 22908.
Adherent murine stromal cells support long-term in vitro lymphopoiesis or
myelopoiesis dependent on the culture conditions used. A cell line, TC-1,
isolated from long-term liquid murine marrow cultures under conditions
approaching those permissive for lymphoid growth, has been found to produce
an activity that acts synergistically with interleukin- 3 (IL-3) or
colony-stimulating factor-1 (CSF-1) to stimulate in vitro myeloid colonies,
but which has no intrinsic colony-stimulating activity. We report here the
presence of multiple growth factors in conditioned medium (CM) from the
TC-1 line, including granulocyte- macrophage colony-stimulating factor
(GM-CSF) (bioassay with antibody blocking and messenger RNA [mRNA]
analysis), granulocyte CSF (G-CSF) and IL-4 (factor-dependent cell line
bioassay), and CSF-1 (radioimmunoassay, mRNA) along with a pre-B cell
inducing activity, which appears separate from these CSFs and segregates
with the myeloid synergizing activity through anion exchange, sizing, and
Conconavalin A chromatography. Because these activities are not yet
purified to homogeneity, their identity or lack of identity remains an open
question. Assays of TC-1 CM or cellular mRNA analysis have given negative
results for IL-1, IL-2, IL-3, IL-6, and IL-7, and IL-6 does not stimulate
pre-B cells in this assay. However, IL-4 and G-CSF do stimulate in vitro
induction of pre-B cells from pre-B and B-cell- depleted Balb/C marrow and
are present in CM by selective cell line assay. A monoclonal antibody to
IL-4 that inhibited its pre-B inducing activity did not inhibit pre-B
inducing activity of TC-1 CM. These data suggest the existence of a unique
synergizing and pre-B inducing factor(s) in TC-1 CM. Given the known
capacity of subliminal levels of growth factors to act synergistically, an
alternate possibility is that these biologic phenomena represent the
actions of low concentrations of growth factors acting synergistically and
possibly associated with some core protein.
Volume 75,
Issue 11,
pp. 2130-2136,
06/01/1990
Copyright © 1990 by The American Society of Hematology
