All-trans-retinoic acid counteracts endothelial cell procoagulant activity
induced by a human promyelocytic leukemia-derived cell line (NB4)
A Falanga, M Marchetti, S Giovanelli and T Barbui
Hematology Division, Ospedali Riuniti, Bergamo, Italy.
Therapy with all-trans-retinoic acid (ATRA) can rapidly improve the
coagulopathy of acute promyelocytic leukemia (APL). This study was designed
to evaluate whether the APL cell line NB4 induces the procoagulant activity
(PCA) of human endothelial cells (ECs) in vitro, and whether this property
is modified after ATRA-induced NB4 maturation. EC monolayers were incubated
for 4 hours at 37 degrees C with the conditioned media (CM) of NB4 treated
with 1 mumol/L ATRA (ATRA-NB4-CM) or the vehicle (control-NB4-CM). EC
lysates were tested for PCA. ATRA-NB4-CM induced significantly more
PCA:tissue factor (TF) than control-NB4-CM (P < .01). To identify the
cause of TF induction, interleukin (IL)-1 beta antigen levels were measured
in CM samples. ATRA-NB4-CM contained significantly more IL-1 beta than
control-NB4-CM. EC PCA was significantly inhibited by an anti-IL-1 beta
antibody. The addition to the media of 10 mumol/L ATRA counteracted the EC
TF expression induced by NB4-CM. These data indicate that ATRA increases
the promyelocyte-induced EC TF, partly through increased IL-1 beta
production. However, ATRA can protect the endothelium from the procoagulant
stimulus of leukemic cells.
Volume 87,
Issue 2,
pp. 613-617,
01/15/1996
Copyright © 1996 by The American Society of Hematology
