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The reciprocal relationship of thrombopoietin (c-Mpl ligand) to changes in
the platelet mass during busulfan-induced thrombocytopenia in the rabbit
DJ Kuter and RD Rosenberg
Department of Biology, Massachusetts Institute of Technology, Cambridge,
USA.
Thrombopoietin (c-Mpl ligand) has recently been purified and is considered
to be the humoral regulator of platelet production. To see whether this
molecule possessed the physiologic characteristics necessary to mediate the
feed-back loop between blood platelets and the bone marrow megakaryocytes,
we determined the relationship between blood levels of thrombopoietin and
changes in the circulating platelet mass. We developed a model of nonimmune
thrombocytopenia in rabbits by the subcutaneous administration of busulfan.
Compared with pretreatment plasma, plasma taken from all thrombocytopenic
rabbits at their platelet nadir contained increased amounts of
thrombopoietin. All of this activity was neutralized by soluble c-Mpl
receptor. We subsequently measured the level of thrombopoietin in the
circulation over the entire time course after the administration of
busulfan. As the platelet mass declined, levels of thrombopoietin increased
inversely and proportionally and peaked during the platelet nadir. With
return of the platelet mass toward normal, thrombopoietin levels decreased
accordingly. When platelets were transfused into thrombocytopenic rabbits
near the time of their platelet count nadir, the elevated levels of
thrombopoietin decreased. In addition, platelets were observed to remove
thrombopoietin from thrombocytopenic plasma in vitro. These results confirm
that thrombopoietin is the humoral mediator of megakaryocytopoiesis and
suggest that the platelet mass may directly play a role in regulating the
circulating levels of this factor.
Volume 85,
Issue 10,
pp. 2720-2730,
05/15/1995
Copyright © 1995 by The American Society of Hematology
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