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Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells
mediates the binding of hematopoietic progenitor cells
PJ Simmons, B Masinovsky, BM Longenecker, R Berenson, B Torok-Storb and WM Gallatin
Division of Clinical Research, Fred Hutchinson Cancer Research Center,
Seattle, WA.
Human bone marrow-derived CD34+ cells were analyzed for the expression of
the beta 1-family of integrin adhesion molecules. Integrin alpha 4 beta 1
was consistently expressed by greater than 90% of CD34+ cells, including
essentially all assayable granulocyte-macrophage colony- forming cells
(CFU-GM) and erythroid bursts (BFU-E) as shown by fluorescence-activated
cell sorting studies. Adhesion of highly enriched CD34+ cells to cultured
allogeneic marrow stromal cells was largely inhibited both by monoclonal
antibody to alpha 4 beta 1 and to vascular cell adhesion molecule-1
(VCAM-1), a ligand for alpha 4 beta 1. VCAM-1 was found to be expressed by
bone marrow stromal elements in vitro both constitutively at low level and
at high levels after treatment with cytokines. Induction of VCAM-1 was
cytokine- and time- dependent with maximum levels being obtained after 4
hours of exposure to a combination of interleukin-4 and tumor necrosis
factor-alpha. Cytokine-induced stromal cells bound threefold higher numbers
of CFU-GM and BFU-E, this increase being abrogated by anti-alpha 4 beta 1
and anti-VCAM-1 antibodies. In addition, the adhesion to stroma of more
immature progenitors, the long-term culture initiating cells, also occurred
through an alpha 4 beta 1/VCAM-1-dependent mechanism. These studies
identify an adhesion mechanism of potential importance in the localization
of primitive progenitors within the hematopoietic microenvironment.
Volume 80,
Issue 2,
pp. 388-395,
07/15/1992
Copyright © 1992 by The American Society of Hematology
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