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The Mpl receptor is expressed in the megakaryocytic lineage from late
progenitors to platelets
N Debili, F Wendling, D Cosman, M Titeux, C Florindo, I Dusanter-Fourt, K Schooley, N Methia, M Charon and R Nador
INSERM U362, Institut Gustave Roussy, Villejuif, France.
The Mpl receptor (Mpl-R) is a cytokine receptor belonging to the
hematopoietin receptor superfamily for which a ligand has been recently
characterized. To study the lineage distribution of Mpl-R in normal
hematopoietic cells, we developed a monoclonal antibody (designated M1
MoAb) by immunizing mice with a soluble form of the human Mpl-R protein.
With few exceptions, Mpl-R was detected by indirect immunofluorescent
analysis on all human leukemic hematopoietic cell lines with pluripotential
and megakaryocytic phenotypes, but not on other cell lines. By
immunoprecipitation and immunoblotting, M1 MoAb recognized a band at 82 to
84 kD corresponding to the expected size of the glycosylated receptor.
Among normal hematopoietic cells, M1 MoAb strongly stained megakaryocytes
(MK) and Mpl-R was detected on platelets by indirect immunofluorescence
staining or immunoblotting. On purified CD34+ cells, less than 2% of the
population was stained, but the labeling was weak and just above the
threshold of detection. However, dual-labeling with the M1 and antiplatelet
glycoprotein MoAbs showed that most Mpl-R+/CD34+ cells coexpressed CD41a,
CD61, or CD42a, suggesting that cell surface appearance of Mpl-R and
platelet glycoproteins could be coordinated. M1-positive and M1-negative
subsets were sorted from purified CD34+ cell populations. Colony assays
showed that the absolute number of hematopoietic progenitors was extremely
low and no primitive progenitors were present in the CD34+/Mpl-R+ fraction.
However, this cell fraction was significantly enriched in low proliferative
colony-forming units-MK. When the CD34+/Mpl-R+ fraction was grown in liquid
culture containing human aplastic serum and a combination of growth
factors, mature MK were seen as early as day 4, whereas the predominant
cell population was erythroblasts on day 8. Similar data were also obtained
with the CD34+/Mpl-R- fraction with, however, a delay in the time of
appearance of both MK and erythroblasts. In conclusion, Mpl-R is a cytokine
receptor restricted to the MK cell lineage. Its expression is low on CD34+
cells and these cells mainly correspond to late MK progenitors and
transitional cells. These data indicate that the action of the Mpl-R ligand
might predominate during the late stages of human MK differentiation.
Volume 85,
Issue 2,
pp. 391-401,
01/15/1995
Copyright © 1995 by The American Society of Hematology
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