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Hepatocyte growth factor is constitutively produced by human bone marrow
stromal cells and indirectly promotes hematopoiesis
K Takai, J Hara, K Matsumoto, G Hosoi, Y Osugi, A Tawa, S Okada and T Nakamura
Department of Pediatrics, Osaka University School of Medicine, Japan.
Bone marrow (BM) stromal cells are required for normal hematopoiesis. A
number of soluble factors secreted by these cells that mediate
hematopoiesis have been characterized. However, the mechanism of
hematopoiesis cannot be explained solely by these known factors, and the
existence of other, still unknown stromal factors has been postulated. We
showed that hepatocyte growth factor (HGF) is one such cytokine produced by
human BM stromal cells. BM stromal cells were shown to constitutively
produce HGF and also to express the c-MET/HGF receptor. The production of
HGF was enhanced by addition of heparin and phorbol ester. Dexamethasone
and tumor growth factor-beta (TGF-beta) inhibited the production of HGF.
Interleukin-1 alpha (IL-1 alpha) tumor necrosis factor-alpha (TNF-alpha),
and N6,2'-o-dibutyryl-adenosine- 3':5'-cyclic monophosphate (dbc-AMP)
showed no obvious influence on HGF production. Western blot analysis of HGF
derived from BM stromal cells showed two bands at 85 and 28 kD
corresponding to native and variant HGF, respectively. Addition of
recombinant HGF significantly promoted the formation of burst-forming
unit-erythroid (BFU-E) and colony- forming unit-granulocyte erythroid
macrophage (CFU-GEM) by BM mononuclear cells in the presence of
erythropoietin and granulocyte- macrophage colony-stimulating factor
(GM-CSF), but the formation of CFU- GM was not modified. However, HGF had
no effects on colony formation by purified CD34+ cells. Within BM
mononuclear cells, c-MET was expressed on a proportion of cells (CD34-,
CD33+, CD13+, CD14+, and CD15+), but was not found on CD34+ cells. We
conclude that HGF is constitutively produced by BM stromal cells and that
it enhances hematopoiesis. In addition, expression of c-MET on the stromal
cells suggests the presence of an autocrine mechanism, operating through
HGF, among stromal cells.
Volume 89,
Issue 5,
pp. 1560-1565,
03/01/1997
Copyright © 1997 by The American Society of Hematology
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