Interaction of human bone marrow fibroblasts with megakaryocytes: role of the c-kit ligand.
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.
Avraham
H
H
Department of Medicine, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215.
Scadden
D T
DT
Chi
S
S
Broudy
V C
VC
Zsebo
K M
KM
Groopman
J E
JE
D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004261:DNA Replication / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D012313:RNA / Q000032:analysis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D019089:Stem Cell Factor; D013936:Thymidine / Q000378:metabolism
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D015850:Interleukin-6; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D019089:Stem Cell Factor; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D013936:Thymidine