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Mast cells as targets of pimecrolimus.
[cutaneous mastocytosis]
Mast
cells
,
the
multi-
functional
secretory
cells
,
are
the
pivotal
effector
cells
in
immune
response
,
and
contribute
to
the
pathogenesis
of
many
diverse
diseases
,
like
asthma
and
mastocytosis
,
by
releasing
numerous
proinflammatory
mediators
.
Pimecrolimus
(
SDZ
ASM
981
)
is
a
derivative
of
the
macrolactam
ascomycin
and
is
a
member
of
the
calcineurin
inhibitor
class
of
immunosuppressors
.
It
inhibits
the
calcineurin-dependent
activation
of
nuclear
factor
of
activated
T
cells
and
the
expression
of
a
number
of
proinflammatory
cytokines
in
turn
.
Pimecrolimus
has
high
and
selective
anti-
inflammatory
activity
within
the
skin
,
and
with
much
lower
potential
to
affect
local
and
systemic
immune
responses
.
Therefore
it
has
been
widely
used
for
treatment
of
various
inflammatory
skin
diseases
.
It
has
a
cellselective
mode
of
action
,
and
mast
cells
are
its
specific
target
cells
.
Pimecrolimus
inhibits
the
release
of
both
preformed
and
de
novo
synthesized
mediators
from
activated
mast
cells
and
inhibits
accumulation
of
mast
cells
by
inducing
apoptosis
.
Several
experimental
and
clinical
reports
have
demonstrated
the
successful
application
of
pimecrolimus
and
other
calcineurin
inhibitors
,
such
as
tacrolimus
and
cyclosporine
A
,
to
treat
mastocytosis
,
a
spectrum
of
disorders
characterized
by
mast
cell
hyperplasia
,
especially
cutaneous
mastocytosis
.
These
new
findings
suggest
that
pimecrolimus
and
other
calcineurin
inhibitors
may
be
a
novel
and
effective
therapeutic
approach
for
mast
cell-associated
diseases
such
as
asthma
and
mastocytosis
.
Diseases
Validation
Diseases presenting
"a spectrum of disorders characterized by mast cell hyperplasia"
symptom
cutaneous mastocytosis
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