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Effects of the stem cell factor, c-kit ligand, on human megakaryocytic
cells
H Avraham, E Vannier, S Cowley, SX Jiang, S Chi, CA Dinarello, KM Zsebo and JE Groopman
Division of Hematology/Oncology, New England Deaconess Hospital, Boston, MA
02215.
The kit ligand (KL), also termed stem cell factor (SCF), is a recently
discovered hematopoietic growth factor that augments response of early
progenitor cells to other growth factors and supports proliferation of
continuous mast cell lines. Histological studies suggest that the receptor
for SCF/KL, the c-kit proto-oncogene product, is present in bone marrow
megakaryocytes. We studied the effects of SCF/KL on immortalized human
megakaryocytic cell lines (CMK, CMK6, and CMK11-5) and on isolated human
marrow megakaryocytes. Human SCF/KL alone or in combination with the
hematopoietic growth factors, interleukin-3 (IL- 3), granulocyte-macrophage
colony-stimulating factor (GM-CSF), and IL- 6, stimulated proliferation of
these megakaryocytic cell lines. SCF/KL treatment did not alter expression
of gpIb, gpIIb/IIIa, LFA-1, ICAM-1, or GMP-140 in CMK cells. No effect on
ploidy was observed. Furthermore, human SCF/KL induced expression of IL-1
alpha, IL-1 beta, IL-2, and IL- 6 in CMK cells. In a fibrin clot system,
SCF/KL modestly potentiated megakaryocyte colony formation when added alone
to cultures containing CD34+, DR+ bone marrow cells. Addition of SCF/KL
with IL-3 or GM-CSF to these cultures resulted in a more marked marrow
megakaryocytic cells. SCF/KL may directly affect megakaryocytopoiesis, as
well as secondarily modulate hematopoiesis through induction of cytokines
in target cells.
Volume 79,
Issue 2,
pp. 365-371,
01/15/1992
Copyright © 1992 by The American Society of Hematology
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