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Interaction of human bone marrow fibroblasts with megakaryocytes: role of
the c-kit ligand
H Avraham, DT Scadden, S Chi, VC Broudy, KM Zsebo and JE Groopman
Department of Medicine, New England Deaconess Hospital, Harvard Medical
School, Boston, MA 02215.
Human kit ligand (KL), also known as stem cell factor (SCF), steel factor,
or mast cell growth factor, is a recently identified hematopoietic growth
factor whose receptor is the product of the c-kit proto-oncogene.
Alternative splicing of the pre-mRNA of KL/SCF results in secreted and
membrane-bound forms of the protein. We and others have recently shown that
the c-kit gene product is expressed on human megakaryocytes and that
soluble KL/SCF in combination with granulocyte- macrophage
colony-stimulating factor, interleukin-3 (IL-3), or IL-6 increased
megakaryocyte progenitor colony formation (CFU-MEG) and stimulated mature
megakaryocytes. Here we show that adhesion of human megakaryocytes to bone
marrow stromal fibroblasts, which express the membrane-bound form of KL/SCF
(mKL/SCF), is mediated in part by the interaction between mKL/SCF and the
c-kit protein. This interaction also results in marrow
fibroblast-stimulated proliferation but not an increase in ploidy of
megakaryocytes; when the two cell types were separated by a transoluble
membrane, proliferation did not occur. Adhesion and proliferation of human
megakaryocytes to an immortalized murine stromal cell line SI/SI lacking
the KL/SCF gene was impaired, whereas transfection of SI/SI cells with
human mKL/SCF significantly increased both adhesion and proliferation.
Marrow stromal fibroblast mKL/SCF may serve both as an adhesion structure
and as a growth- potentiating factor for megakaryocytes in the bone marrow.
Volume 80,
Issue 7,
pp. 1679-1684,
10/01/1992
Copyright © 1992 by The American Society of Hematology
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