INVESTIGADORES
SCHATTNER Mirta Ana
artículos
Título:
Expression and functionality of type I interferon receptor in the megakaryocytic lineage
Autor/es:
NEGROTTO S; JAQUENOD DE GIUSTI C; LAPPONI MJ; ETULAIN J; RIVADENEYRA L; POZNER R; GOMEZ RM; SCHATTNER M
Revista:
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Año: 2011 vol. 9 p. 2477 - 2485
ISSN:
1538-7933
Resumen:
Background: Type I interferons (IFN-I) negatively
regulate megakaryo/thrombopoiesis. However, expression of
the IFN-I receptor (IFNAR) in the megakaryocytic lineage is
poorly characterized. Objectives: To study the expression and
functionality of IFNAR in the megakaryocytic lineage. Methods
and results: Although IFNAR mRNA was found in every
cell type studied, its protein expression showed differences
between them. According to flow cytometry and immunofluorescence,
IFNAR1 was observed in Meg-01, Dami, CD34+
cells and megakaryocytes, but not in proplatelets or platelets.
Immunoblotting assays showed that IFNAR1 and IFNAR2
were highly expressed in all cell types, except in platelets where it
was barely detectable. Regarding IFNAR1, 130- and 90-kDa
bands were detected in Meg-01 andDami, whereas 130- and 60-
kDa bands were found in CD34+ cells and megakaryocytes.
Activation of megakaryocytic IFNAR by IFN-b induced
pSTAT1/2 and upregulated the antiviral genes IRF7 and
MXA. The latter response was completely suppressed by
IFNAR blockade. In contrast, the low levels of IFNAR in
platelets were not functional as pSTAT1/2, aggregation and Pselectin
expression were not induced by IFN-I. In addition,
megakaryocytes increased IFN-I transcript levels and produced
IFN-b upon stimulation with PolyI:C, a synthetic dsRNA that
mimics viral infection. Conclusions: Early progenitors and
mature megakaryocytes, but not platelets, express functional
IFNAR and synthetize/release IFN-b, revealing not only that
megakaryo/thrombopoiesis regulation by IFN-I is associated
with a specific interaction with its receptor, but also that
megakaryocytesmay play a role in the antiviral defense by being
both IFN producers and responders.