Hepatology Communications,
Год журнала:
2019,
Номер
3(6), С. 730 - 743
Опубликована: Апрель 22, 2019
Inflammation
is
a
hallmark
of
virtually
all
liver
diseases,
such
as
cancer,
fibrosis,
nonalcoholic
steatohepatitis,
alcoholic
disease,
and
cholangiopathies.
Liver
macrophages
have
been
thoroughly
studied
in
human
disease
mouse
models,
unravelling
that
the
hepatic
mononuclear
phagocyte
system
more
versatile
complex
than
previously
believed.
mainly
consist
liver-resident
phagocytes,
or
Kupffer
cells
(KCs),
bone
marrow-derived
recruited
monocytes.
Although
both
cell
populations
demonstrate
principal
functions
macrophages,
phagocytosis,
danger
signal
recognition,
cytokine
release,
antigen
processing,
ability
to
orchestrate
immune
responses,
KCs
monocytes
retain
characteristic
ontogeny
markers
remain
remarkably
distinct
on
several
functional
aspects.
While
dominate
macrophage
pool
homeostasis
("sentinel
function"),
monocyte-derived
prevail
acute
chronic
injury
("emergency
response
team"),
making
them
an
interesting
target
for
novel
therapeutic
approaches
disease.
In
addition,
recent
data
acquired
by
unbiased
large-scale
techniques,
single-cell
RNA
sequencing,
unraveled
unrecognized
complexity
murine
polarization
abilities,
far
beyond
old
dogma
inflammatory
(M1)
anti-inflammatory
(M2)
macrophages.
Despite
tremendous
progress,
numerous
challenges
deciphering
full
spectrum
activation
its
implication
either
promoting
progression
repairing
injured
tissue.
Being
aware
heterogeneity
origin
function
crucial
importance
when
studying
developing
interventions,
defining
macrophage-based
prognostic
biomarkers,
designing
clinical
trials.
Growing
knowledge
gene
expression
modulation
emerging
technologies
drug
delivery
may
soon
allow
shaping
toward
orchestrating
beneficial
rather
detrimental
responses.
Cellular and Molecular Immunology,
Год журнала:
2016,
Номер
13(3), С. 267 - 276
Опубликована: Апрель 11, 2016
The
human
liver
is
usually
perceived
as
a
non-immunological
organ
engaged
primarily
in
metabolic,
nutrient
storage
and
detoxification
activities.
However,
we
now
know
that
the
healthy
also
site
of
complex
immunological
activity
mediated
by
diverse
immune
cell
repertoire
well
non-hematopoietic
populations.
In
non-diseased
liver,
metabolic
tissue
remodeling
functions
require
elements
inflammation.
This
inflammation,
combination
with
regular
exposure
to
dietary
microbial
products,
creates
potential
for
excessive
activation.
this
microenvironment,
hepatic
system
tolerates
harmless
molecules
while
at
same
time
remaining
alert
possible
infectious
agents,
malignant
cells
or
damage.
Upon
appropriate
activation
challenge
pathogens
damage,
mechanisms
resolve
inflammation
are
essential
maintain
homeostasis.
Failure
clear
'dangerous'
stimuli
regulate
appropriately
activated
leads
pathological
disrupted
homeostasis
characterized
progressive
development
fibrosis,
cirrhosis
eventual
failure.
Hepatic
inflammatory
therefore
have
spectrum
roles
adult
liver;
they
and,
when
dysregulated,
key
drivers
pathology
associated
chronic
infection,
autoimmunity
malignancy.
review,
explore
changing
perception
mediators
normal
propose
targeting
liver-specific
regulation
pathways
therapeutic
approach
treat
disease.
European Journal of Immunology,
Год журнала:
2019,
Номер
49(10), С. 1457 - 1973
Опубликована: Окт. 1, 2019
These
guidelines
are
a
consensus
work
of
considerable
number
members
the
immunology
and
flow
cytometry
community.
They
provide
theory
key
practical
aspects
enabling
immunologists
to
avoid
common
errors
that
often
undermine
immunological
data.
Notably,
there
comprehensive
sections
all
major
immune
cell
types
with
helpful
Tables
detailing
phenotypes
in
murine
human
cells.
The
latest
techniques
applications
also
described,
featuring
examples
data
can
be
generated
and,
importantly,
how
analysed.
Furthermore,
tips,
tricks
pitfalls
avoid,
written
peer-reviewed
by
leading
experts
field,
making
this
an
essential
research
companion.
Nature Communications,
Год журнала:
2015,
Номер
6(1)
Опубликована: Март 26, 2015
Neutrophil
extracellular
traps
(NETs)
composed
of
DNA
decorated
with
histones
and
proteases
trap
kill
bacteria
but
also
injure
host
tissue.
Here
we
show
that
during
a
bloodstream
infection
methicillin-resistant
Staphylococcus
aureus,
the
majority
are
sequestered
immediately
by
hepatic
Kupffer
cells,
resulting
in
transient
increases
liver
enzymes,
focal
ischaemic
areas
robust
neutrophil
infiltration
into
liver.
The
neutrophils
release
NETs
vasculature,
which
remain
anchored
to
vascular
wall
via
von
Willebrand
factor
reveal
significant
elastase
(NE)
proteolytic
activity.
Importantly,
DNase
although
very
effective
at
removal,
somewhat
inhibiting
NE
activity,
fails
remove
from
vessel
only
partly
reduces
injury.
By
contrast,
inhibition
NET
production
as
modelled
PAD4-deficiency,
or
prevention
formation
activity
NE(-/-)
mice
prevent
collateral
tissue
damage.
