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Relative reactivity of platelets from thrombopoietin- and interleukin-6-
treated dogs
J Peng, P Friese, RF Wolf, P Harrison, T Downs, S Lok, GL Dale and SA Burstein
Department of Medicine, University of Oklahoma Health Sciences Center,
Oklahoma City 73190, USA.
Previous reports have shown that interleukin-6 (IL-6) enhances the
responsiveness of platelets to thrombin stimulation and has modest
thrombocytopoietic effects in vivo. Thrombopoietin (TPO; mpl ligand) has
been shown to have dramatic thrombocytopoietic effect in vivo, but little
is known of its capacity to alter platelet function. In this study, a
direct comparison of the effects of IL-6 and TPO on platelet function in
dogs has been performed, with modest doses of TPO (1 microgram/kg/d) chosen
to match or moderately exceed the platelet counts achieved with IL-6 (40
micrograms/kg/d) for 10 days. Platelet responsiveness to thrombin
stimulation was assessed in TPO-treated, IL- 6-treated, and control dogs by
flow cytometric measurement of P- selectin expression. On day 5, the dose
of thrombin promoting half maximal stimulation (EC50) of platelets was not
significantly changed in TPO-treated dogs, whereas in IL-6-treated dogs the
EC50 decreased to 73.1% +/- 6.1% (mean +/- 1 SD; n = 5) of control values
(P < 0.01). These experiments were performed on both gel-filtered
platelets and washed whole blood, indicating that the observed changes in
EC50 were caused by cytokine-mediated alteration of platelets rather than
plasma components. Because it has been shown that thiazole orange
specifically labels a subpopulation of dog platelets that is less than 24
hours old, the thrombin responsiveness of these young, newly synthesized
platelets was determined. The EC50 of thiazole orange-positive platelets
from IL- 6-treated dogs decreased dramatically by day 5 to 46.5% +/- 13.1%
(n = 4) of control values (P < 0.001), whereas TPO-treated dogs did not
significantly change. When TPO was directly incubated with platelets ex
vivo, no effects on either thrombin-mediated P-selectin expression or
adenosine diphosphate-induced fibrinogen binding were observed. These data
show that IL-6 alters platelet function, as measured by reactivity to
thrombin, whereas TPO does not. This divergence in function is observed
even though TPO is equally, or more, effective at promoting platelet
production under these experimental conditions.
Volume 87,
Issue 10,
pp. 4158-4163,
05/15/1996
Copyright © 1996 by The American Society of Hematology
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