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Human megakaryocyte stimulation of proliferation of bone marrow fibroblasts
H Castro-Malaspina, EM Rabellino, A Yen, RL Nachman and MA Moore
Human marrow cells were processed sequentially by density centrifugation
and by velocity sedimentation in serum-free Percoll gradients in order to
purify megakaryocytes and to determine if these cells are the source of the
growth factor derived from platelets. Cell homogenates were made from the
resulting fractions and tested for growth-promoting activity(ies) in 3T3
cells and in well characterized human marrow fibroblasts. Growth was
evaluated by 3H-TdR incorporation and changes in DNA cell content, as
measured by flow microfluorometry. The highest mitogenic activity was
derived from homogenates of low density (less than 1.050 g/cu cm), rapidly
sedimenting cells. This fraction contained the highest percentage of
megakaryocytes. The assessment of growth-promoting activity(ies) derived
from various megakaryocyte-enriched marrow cell homogenates containing
different proportions of megakaryocytes demonstrated a positive correlation
between the number of megakaryocytes and their stimulatory capacity as
determined by 3H-TdR uptake. The growth-promoting activities elicited from
homogenates of platelets and marrow fractions enriched for megakaryocytes
were similar. The dose--response curves for both were parallel, and they
were both temperature resistant and trypsin sensitive. These findings
implicate megakaryocytes as a source of the growth factor derived from
platelets and suggest that megakaryocytes may play a role in the
pathogenesis of the marrow fibrosis observed in myeloproliferative
disorders by stimulating fibroblast proliferation and collagen secretion.
Volume 57,
Issue 4,
pp. 781-787,
04/01/1981
Copyright © 1981 by The American Society of Hematology
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