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Fibrinogen potentiates the effect of interleukin-3 on early human
hematopoietic progenitors
YQ Zhou, JP Levesque, A Hatzfeld, AA Cardoso, ML Li, P Sansilvestri and J Hatzfeld
Laboratoire de Biologie Cellulaire et Moleculaire des Facteurs de
Croissance, Centre National de la Recherche Scientifique, Villejuif,
France.
The effect of human fibrinogen on the proliferation of purified SBA- CD34+
human bone marrow progenitors was investigated in clonal cultures.
Fibrinogen alone or in combination with erythropoietin had no significant
effect. However, in the presence of recombinant human interleukin-3 (IL-3),
fibrinogen increased significantly in a dose- dependent manner the number
of mixed and burst-forming unit-ethrocyte-- derived colonies, whereas the
number of other colonies did not significantly change. In the presence of
fibrinogen, low concentrations of IL-3 (0.17 U/mL) produced three times
more mixed colonies than without fibrinogen, reaching the number of
colonies obtained with optimal concentrations of IL-3 (1.67 U/mL).
Fibrinogen fragment D had the same effect in the presence of IL-3 as intact
fibrinogen, whereas fibrinogen fragment E and human collagen IV did not.
This effect was not mediated by integrins, because peptides or monoclonal
antibodies that block fibrinogen binding on integrins alpha IIb beta 3,
alpha v beta 3 (RGD-peptides), alpha m beta 2 (OKM-1), and alpha x beta 2
(HC1/1) did not affect the observed mitogenic effect. The mitogenic effect
of fibrinogen and its D fragment was not mediated by induction of IL-6 or
granulocyte--colony-stimulating factor secretion, because it was not
inhibited by blocking antisera against these two growth factors. Our
results indicate that fibrinogen potentiates the effect of IL-3 on
primitive hematopoietic progenitors and suggest that the mitogenic effect
of fibrinogen could be mediated via a specific mitogenic receptor that does
not belong to the integrin family.
Volume 82,
Issue 3,
pp. 800-806,
08/01/1993
Copyright © 1993 by The American Society of Hematology

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