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Platelet factor 4 inhibits human megakaryocytopoiesis in vitro
ZC Han, L Sensebe, JF Abgrall and J Briere
Department of Hematology, Augustin Morvan Hospital, Brest University School
of Medicine, France.
Platelet factor 4 (PF4) is a multifunctional protein specific to platelets,
synthesized in megakaryocytes and stored in alpha granules. This report of
our work shows that PF4 potently inhibits human megakaryocyte colony
formation in vitro. Colony formation by megakaryocyte progenitor cells from
normal bone marrows was studied using the plasma clot culture system and
indirect immunoperoxidase staining. Nonadherent mononuclear cells were
co-cultured with various concentrations (0 to 20 micrograms/mL) of highly
purified human PF4. Statistically significant inhibition of three classes
of megakaryocyte progenitor cells, the mixed colony forming
unit-megakaryocytes (mCFU- MK), the burst forming unit-megakaryocytes
(BFU-MK), and the colony forming unit-megakaryocytes (CFU-MK), was seen at
a PF4 concentration of 2.5 micrograms/mL or greater. PF4 had no effect on
erythroid (BFU-E) and granulocyte/macrophage (CFU-GM) colony formation
except at high concentration (5 micrograms/mL for BFU-E and 10
micrograms/mL for CFU- GM). When a concentration of 5 micrograms/mL PF4 was
added at various time points during marrow culture, a reduction of
megakaryocyte colony formation also occurred. In the presence of PF4 2.5
micrograms or 5 micrograms/mL, the percentage of mature type of colonies
was found to be decreased compared with cultures with no added PF4. These
data demonstrate that PF4 inhibits both proliferation and maturation of
megakaryocyte progenitor cells in vitro and suggest that PF4 may play a
role in autoregulating human megakaryocytopoiesis.
Volume 75,
Issue 6,
pp. 1234-1239,
03/15/1990
Copyright © 1990 by The American Society of Hematology
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