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Originally published In Press as doi:10.1074/jbc.M110729200 on January 30, 2002
J. Biol. Chem., Vol. 277, Issue 15, 12689-12696, April 12, 2002
Extracellular mRNA Induces Dendritic Cell Activation by
Stimulating Tumor Necrosis Factor- Secretion and Signaling through a
Nucleotide Receptor*
Houping
Ni ,
John
Capodici ,
Georgetta
Cannon ,
Didier
Communi§,
Jean-Marie
Boeynaems§,
Katalin
Karikó¶, and
Drew
Weissman
From the Divisions of Infectious Diseases and
¶ Neurosurgery, University of Pennsylvania, Philadelphia,
Pennsylvania 19104 and the § Institute of Interdisciplinary
Research and Department of Medical Chemistry, School of Medicine,
Erasme Hospital, Université Libre de Bruxelles, Brussels
1070, Belgium
We previously demonstrated that dendritic cell
(DC) pulsing with antigen-encoded mRNA resulted in the loading of
both major histocompatibility complex class I and II antigen
presentation pathways and the delivery of an activation signal.
Coculture of mRNA-pulsed DC with T cells led to the induction of a
potent primary immune response. DC, in addition to recognizing foreign
antigens through pattern recognition receptors, also must respond to
altered self, transformed, or intracellularly infected cells.
This occurs through cell surface receptors that recognize products of
inflammation and cell death. In this report, we characterize two
signaling pathways utilized by extracellular mRNA to activate DC.
In addition, a novel ligand, poly(A), is identified that mediates
signaling through a receptor that can be inhibited by pertussis toxin
and suramin and can be desensitized by ATP and ADP, suggesting a
P2Y type nucleotide receptor. The role of this signaling activity in
vaccine design and the potential effect of mRNA released by damaged
cells in the induction of immune responsiveness is discussed.
*
This work was supported by NHLBI, National Institutes of
Health (NIH) Grant R01-HL-62060-1 and by NIAID, NIH Grant
R21-AI-45318-01A1.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Division of
Infectious Diseases, University of Pennsylvania, 522B Johnson
Pavilion, Philadelphia, PA 19104. Tel.: 215-614-0291; Fax:
215-349-5111; E-mail: dreww@mail.med.upenn.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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