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Stem cell factor modulates avidity of alpha 4 beta 1 and alpha 5 beta 1
integrins expressed on hematopoietic cell lines
NL Kovach, N Lin, T Yednock, JM Harlan and VC Broudy
School of Medicine, Division of Hematology, University of Washington,
Seattle.
Interactions between hematopoietic cells and bone marrow (BM) stroma,
composed of extracellular matrix and stromal cells, are crucial for
hematopoiesis. Integrins facilitate these interactions by mediating
adherence of hematopoiesis. Integrins facilitate these interactions by
mediating adherence of hematopoietic cells to both the extracellular matrix
and stromal cells. Marrow stromal cells secrete a variety of growth
factors, including stem cell factor (SCF). Because treatment with SCF in
vivo mobilizes primitive hematopoietic cells from the BM, we investigated
the effect of the growth factor SCF of hematopoietic cell adhesion. These
studies show that SCF modulates adhesive function in a dose- and
time-dependent manner, but does not modulate expression of the integrins
alpha 4 beta 1 and alpha 5 beta 1 in the SCF- responsive cell line MO7E.
Treatment of MO7E cells with SCF (200 ng/mL) produced a transient increase
in adherence to cytokine-activated human umbilical vein endothelial cells
(HUVECs) or to vascular cell adhesion molecule 1 (VCAM-1)-transfected
Chinese hamster ovary (CHO) cells with peak adhesion at 30 minutes and
return to baseline by 60 to 90 minutes. This increase in adhesion was
paralleled by increased binding of the beta 1 activation-dependent
monoclonal antibody (MoAb) 15/7, as determined by flow cytometry. However,
prolonged incubation of MO7E with SCF induced a marked decrease in
integrin-mediated adherence, with maximal inhibition by 24 hours. No change
in expression of integrins, as determined by flow cytometry, was observed
with short- or long-term incubation with SCF. SCF-treated cells were still
able to respond to phorbol esters and to the activating beta 1 MoAb 8A2
with increased adherence, but not to the level seen in control cells. This
suggests that a subpopulation of expressed alpha 4 beta 1 and alpha 5 beta
1 integrins is disengaged by prolonged incubation with SCF.
Volume 85,
Issue 1,
pp. 159-167,
01/01/1995
Copyright © 1995 by The American Society of Hematology
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