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Blood, Vol. 93 No. 9 (May 1), 1999:
pp. 2859-2866
High-Level Expression of Mpl in Platelets and Megakaryocytes Is
Independent of Thrombopoietin
Karine Cohen-Solal,
Natacha Vitrat,
Monique Titeux,
William Vainchenker, and
Françoise Wendling
From the INSERM U 362, Institut Gustave Roussy, Villejuif, France.
Thrombopoietin (TPO) is a hematopoietic growth factor that regulates
megakaryocytopoiesis and platelet production through binding to its
receptor, Mpl, encoded by the c-mpl proto-oncogene. Circulating
levels of TPO are regulated by receptor-mediated uptake and
degradation. To better understand this mode of TPO regulation, we
examined whether expression of Mpl was regulated by its ligand. Using
RNase protection analysis, we found no differences in the levels of
c-mpl transcripts in megakaryocytes (MKs) produced in vitro
either in the presence or absence of TPO and in platelets (PLTs)
obtained from mice hyperstimulated in vivo by ectopic secretion of TPO.
Similarly, Western blot analysis of MKs produced in the presence or
absence of TPO showed no difference in Mpl levels. Levels of Mpl,
GpIIb, or P-selectin were virtually identical in platelet lysates
obtained from normal, TPO knockout and mildly TPO-stimulated mice. In
contrast, the expression of Mpl was significantly reduced in PLTs from
severely thrombocythemic mice. These results show that TPO does not
have a major effect on the transcription or translation of Mpl.
However, they do suggest that an excess of circulating TPO can lead to
the disappearance of Mpl from PLTs via catabolism.
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