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【Cancer Research】编译：肿瘤细胞源性一氧化氮性
Tumor Cell-Derived Nitric Oxide Is Involved in the Immune-Rejection of an
Immunogenic Murine Lymphoma
CANCER RESEARCH 64, 152–161, January 1, 2004
ABSTRACT
The roles played by host-derived nitric oxide (NO) in the growth and
subsequent immune rejection of a immunogenic murine lymphoma were
investigated by growing the tumor in mice in which the gene for either
inducible NO synthase (iNOS) or endothelial NOS (eNOS) had been
ablated. This showed that NO from tumor-infiltrating host cells had no
significant effect on either tumor growth or immune rejection, although
measurements of tumor nitrite levels and protein nitration showed that
there had been significant NO production in the rejected tumors, in both
the eNOS and iNOS knockout mice. Inhibition of both tumor and host
NOS activities, with an iNOS-selective inhibitor (1400W), a nonselective
NOS inhibitor [N-nitro-L-arginine methyl ester (L-NAME)], or scavenging
NO with a ruthenium-based scavenger, significantly delayed tumor
rejection, while having no appreciable effect on tumor growth. Incubation
of tumor cells with medium taken from cultured splenocytes, that had
been isolated from immunized animals and activated by incubating them
with irradiated tumor cells, resulted in an increase in tumor cell NOS
activity and an increase in tumor cell apoptosis, which could be inhibited
using L-NAME. We propose that, during the immune rejection of this
tumor model, there is induction of tumor NOS activity by cytokines
secreted by activated lymphocytes within the tumor and that this results
in increased levels of tumor NO that induce tumor cell apoptosis and
facilitate immune rejection of the tumor.
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作者:admin@医学,生命科学 2011-02-15 05:11
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