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Expression and physiologic significance of Kit ligand and stem cell
tyrosine kinase-1 receptor ligand in normal human CD34+, c-Kit+ marrow
cells
MZ Ratajczak, WI Kuczynski, DL Sokol, JS Moore, CH Pletcher and AM Gewirtz
Department of Pathology, University of Pennsylvania School of Medicine,
Philadelphia 19104, USA.
To determine the potential role of autocrine growth factor production in
regulating primitive human hematopoietic cell development, we examined
highly purified CD34+, c-Kit+ marrow mononuclear cells for expression of
c-Kit ligand (KL) and stem cell tyrosine kinase 1 (stk1) ligand (STK1-L).
Normal marrow mononuclear cells coexpressing CD34 and c-Kit were isolated
by a combination of immunomagnetic bead isolation and
fluorescence-activated cell sorting. Purified cells were then screened for
expression of KL and stk1-L mRNA using a sensitive reverse
transcription-polymerase chain reaction method. Using this approach,
expression of both cytokine genes at the mRNA level was found in this
highly enriched cell population. We then examined the functional
significance of these mRNAs by inhibiting their expression with antisense
(AS) oligodeoxynucleotides (ODN). In comparison to untreated or control ODN
treated cells, inhibition of KL led to a 70% and 89% inhibition in
burst-forming unit-erythroid (BFU-E) and colony-forming unit-Mix (CFU-Mix)
colonies but had no significant effect on CFU- granulocyte-macrophage
(CFU-GM) cloning efficiency. In contrast, inhibition of STK1-L alone had no
effect on colony formation. However, when STK1-L AS ODN was combined with
KL AS ODN, additive inhibition of CFU-GM and CFU-MIX but not of BFU-E
colonies was observed. These findings, along with those of our previous
studies showing inhibition of primitive hematopoietic cell growth with
antisense ODN directed towards the stk1 receptor, suggest the possibility
that both receptor/ligand axes regulate primitive hematopoietic cell growth
via an autocrine growth loop.
Volume 86,
Issue 6,
pp. 2161-2167,
09/15/1995
Copyright © 1995 by The American Society of Hematology
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