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*
Cellular and Molecular Immunology Group, Antigenics, Inc., Woburn, MA 01801; and
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030
NO is a cytotoxic and immunomodulatory cytokine produced by
macrophages and dendritic cells. We show that stimulation of murine and
human macrophages with the heat shock proteins gp96 and hsp70 results
in induction of inducible NO synthase and the production of NO. The
release of NO by monocytes exposed to hsp60 has been documented
previously. Immature, but not mature, dendritic cells respond in the
same manner. The activity of heat shock proteins is relatively
unaffected by an antagonist of LPS, and is abrogated by heat
denaturation. Macrophages have been shown previously to produce NO in
response to stimulation with IFN-
; stimulation of macrophages with
mixtures of IFN- and gp96 or hsp70 leads to a synergistic production
of NO. The present observations extend the roles of these heat shock
proteins in innate immune responses to another potent and highly
conserved function of APC.
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