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Induction of differentiation of promyelocytic NB4 cells by retinoic acid is
associated with rapid increase in urokinase activity subsequently
downregulated by production of inhibitors
H Tapiovaara, S Matikainen, M Hurme and A Vaheri
Department of Virology, University of Helsinki, Finland.
13-trans retinoic acid (13-trans RA) is an effective inducer of
differentiation of acute promyelocytic (APL) cells both in vivo and in
vitro. It is used in the induction of remission of patients with APL. We
found, by using the promyelocytic NB4 cell line established from a patient
with APL, that the induction of differentiation with RA was accompanied by
modulation of the plasminogen activation system. The expression of
urokinase (uPA) activity was rapidly increased in the growth medium and at
the surface of cells treated with RA. The high uPA activity was
counteracted both in the growth medium and at the cell surface by an
increased plasminogen activator inhibitor (PAI) production and reduction of
uPA synthesis. The expression of uPA receptor and PAI-2 were stimulated and
persisted at 48 hours from RA addition. The simultaneous induction of CD11b
suggests that differentiation results in increased production of both. APL
patients often encounter episodes of disseminated intravascular coagulation
that are associated with secondary fibrinolytic events. Our results suggest
that downregulation of uPA activity results in the decrease of plasmin on
the surface of the differentiated cells, which may reduce the occurrence of
fibrinolytic episodes of patients with APL.
Volume 83,
Issue 7,
pp. 1883-1891,
04/01/1994
Copyright © 1994 by The American Society of Hematology
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