Regulation of human basophil activation; The role of Na+ and Ca2+ in IL-3-induced potentiation of IgE-mediated histamine release from human basophils

Abstract

The release of mediators from human basophils is strongly enhanced by IL-3. However, the signalling pathways of IL-3 are poorly defined in these cells. Since external Ca2+ and Na+ play important regulating roles in histamine release, the possibility that these cations could be involved in the potentiation by IL-3 of the anti-IgE-induced histamine release from human basophils was considered, and it was observed that: (i) IL-3 dramatically decreased the external Ca2+ requirement for IgE-mediated histamine release. However, histamine release from IL-3-treated basophils became only partially independent of external Ca2+, since addition of EGTA in the external medium abolished the effect of IL-3; (ii) decreasing Na+ influx by lowering external Na+ concentration in isosmotic medium inhibited the potentiating effect of IL-3 on IgE-mediated release; (iii) amiloride, an inhibitor of Na+/Ca2+ and Na+/H+ exchanges, and its derivative, benzamil, more specific for Na+/Ca2+ exchanges, inhibited the release potentiated by IL-3. In contrast, the amiloride derivative 5-(N,N-dimethyl)-amiloride, more specific for Na+/H+ exchanges, slightly increased the IL-3-enhanced release. Thus, the decreased requirement for external Ca2+ and the dependence on external Na+, taken with the effect of the Na+/Ca2+ exchange inhibitors, suggest that Na+/Ca2+ exchanges are involved in the IL-3-induced enhancement of IgE-mediated human basophil histamine release.

Full text

Clin
Exp
Immunol
1994;
95:191-194
Regulation
of
human
basophil
activation;
the
role
of
Na+
and
Ca
2+
in
IL-3-induced
potentiation
of
IgE-mediated
histamine
release
from
human
basophils
F.
BEAUVAIS,
K.
ECHASSERIEAU,
C.
BURTIN
&
J.
BENVENISTE
INSERM
U200,
Universite
Paris-Sud,
Clamart,
France
(Acceptedfor
publication
29
September
1993)
SUMMARY
The
release
of
mediators
from
human
basophils
is
strongly
enhanced
by
I
L-3.
However,
the
signalling
pathways
of
IL-3
are
poorly
defined
in
these
cells.
Since
external
Ca2+
and
Na+
play
important
regulating
roles
in
histamine
release,
the
possibility
that
these
cations
could
be
involved
in
the
potentiation
by
IL-3
of
the
anti-IgE-induced
histamine
release
from
human
basophils
was
considered,
and
it
was
observed
that:
(i)
IL-3
dramatically
decreased
the
external
Ca2+
requirement
for
IgE-mediated
histamine
release.
However,
histamine
release
from
IL-3-treated
basophils
became
only
partially
independent
of
external
Ca2
,
since
addition
of
EGTA
in
the
external
medium
abolished
the
effect
of
IL-3;
(ii)
decreasing
Na+
influx
by
lowering
external
Na+
concentration
in
isosmotic
medium
inhibited
the
potentiating
effect
of
IL-3
on
IgE-mediated
release;
(iii)
amiloride,
an
inhibitor
of
Na+/Ca2+
and
Na+/H+
exchanges,
and
its
derivative,
benzamil,
more
specific
for
Na+/
Ca2+
exchanges,
inhibited
the
release
potentiated
by
IL-3.
In
contrast,
the
amiloride
derivative
5-(N,
N-dimethyl)-amiloride,
more
specific
for
Na+/H+
exchanges,
slightly
increased
the
IL-3-enhanced
release.
Thus,
the
decreased
requirement
for
external
Ca2+
and
the
dependence
on
external
Na+,
taken
with
the
effect
of
the
Na+/Ca2+
exchange
inhibitors,
suggest
that
Na+/Ca2+
exchanges
are
involved
in
the
IL-3-induced
enhancement
of
IgE-mediated
human
basophil
histamine
release.
Keywords
basophil
histamine
release
IL-3
Na+
Ca2+
INTRODUCTION
IL-3
is
a
multipotent
lymphokine
which,
among
various
effects,
induces
growth
and
differentiation
of
human
basophils
from
bone
marrow
precursors
[1].
IL-3
is
also
effective
on
mature
cells
and
activates
human
basophils
via
membrane
high-affinity
binding
sites
[2],
thus
increasing
their
adhesiveness
to
endothe-
lial
cells
[3]
and
the
release
of
histamine
and
leucotrienes
induced
by
anti-IgE
or
formyl-methionyl-leucyl-phenylalanine
(fMLP)
[2,4-7].
Moreover,
IL-3
primes
basophils
to
release
histamine
and
leucotrienes
after
challenge
with
C3a,
IL-8
or
paf-acether
(platelet-activating
factor
(PAF))
which
alone
are
not
releasers
[8-10]
or
with
C5a
which
alone
releases
histamine
but
not
leucotrienes
[I
1].
However,
attempts
to
elucidate
the
pathways
involved
in
the
potentiating
effect
of
IL-3
on
basophil
release
remain
rare
[7].
In
a
recent
report,
it
was
shown
that
C5a-induced
leucotriene
C4
synthesis
from
IL-3-primed
human
basophils
was
regulated
by
tyrosine
kinase
and
protein
kinase
C
(PKC)
in
an
opposite
manner
[12].
In
the
present
study
we
explored
the
requirement
Correspondence:
F.
Beauvais,
INSERM
U3
12,
Laboratoire
de
Dermatologie,
H6pital
Henri-Mondor,
51,
Avenue
du
Marechal
de
Lattre
de
Tassigny,
94010
Creteil,
France.
191
for
cations
of
the
IL-3
effect
on
IgE-mediated
basophil
hista-
mine
release,
and
observed
that
IL-3
decreased
the
Ca2+
requirement
for
basophil
histamine
release.
Moreover,
external
Na+
appeared
to
be
necessary
for
the
IL-3
effect.
This
led
us
to
the
hypothesis,
supported
by
the
effect
of
pharmacological
inhibitors,
that
Na+/Ca2+
exchanges
play
a
major
role
in
the
IL-
3
effect
on
human
basophil
histamine
release
induced
by
anti-
IgE.
MATERIALS
AND
METHODS
Reagents
Recombinant
human
IL-3
(Genzyme
Corp.,
Boston,
MA),
goat
Fc-specific
anti-human
IgE
antiserum
(Nordic
Immunological
Labs,
Tilburg,
The
Netherlands),
HEPES,
N-methyl-D-gluca-
mine,
amiloride
(Sigma
Chemical
Co.,
St
Louis,
MO),
fura-2
pentapotassium
salt
(Calbiochem,
La
Jolla,
CA),
and
5-(N,N-
dimethyl)-amiloride
and
benzamil
hydrochloride
(Research
Biochemicals
Inc.,
Natick
MA)
were
obtained
as
mentioned.
EGTA
was
prepared
as
a
stock
solution
(200
mM)
titrated
to
pH
74.

F.
Beauvais
et
al.
Leucocyte
histamine
release
The
release
of
histamine
was
examined
as
previously
described
[13].
Venous
blood
from
healthy
donors
was
collected
on
anticoagulant
and
allowed
to
sediment
with
dextran.
The
leucocyte-rich
layer
was
then
twice
washed
in
HEPES-buffered
isotonic
solution
(NaCI
140
mm,
KC1
2-6
mm,
HEPES
10
mm,
glucose
5
5
mm
pH
7
4).
In
experiments
with
'low
Na+'
saline
solution,
NaCl
was
isosmotically
replaced
with
either
N-methyl-
D-glucamine
or
glucose.
In
the
'low
Na+'
solution,
the
osmolar-
ity
was
between
290
and
300
mOsmol
(Roebling
osmometer;
Bioblock
Scientific,
Strasbourg,
France)
and
Na+
concentra-
tion
(free
ions)
was
4
mM
as
measured
by
indirect
potentiometric
method
(IL
508;
Delhome,
Paris,
France).
Ca2+
concentration
(free
ions)
was
approximately
1
pM
in
saline
solution
before
any
Ca2+
addition,
as
measured
with
the
fura-2
method
(Shimadzu
RF5000
Spectrofluorometer;
Roucaire,
Velizy,
France)
[14].
Leucocytes
were
finally
suspended
at
30-40
basophils/pl
and
aliquoted
in
plastic
tubes.
IL-3,
anti-IgE
antiserum
and
CaCI2
at
defined
concentrations,
or
diluting
buffer
alone
for
controls,
were
added
sequentially
(see
Results).
After
incubation
in
a
water
bath
(370C)
for
the
stated
periods
of
time,
the
tubes
were
centrifuged
(700
g,
20
min)
and
300
pl
of
each
supernatant
were
added
to
an
equal
volume
of
HCI04
0
8
N.
Total
histamine
content
was
assessed
by
adding
HC104
0-8
N
to
an
equal
volume
of
cell
suspension.
After
centrifugation,
the
HCI04
extracts
were
kept
at
4°C
and
histamine
determination
was
performed
using
an
automated
spectrofluorometric
assay
[15].
Percentages
of
histamine
release
were
calculated
as
follows:
100
x
(test
-
con-
trol)/(total
-control),
where
test,
control
and
total
were
the
histamine
contents
measured
in
the
supernatant
in
the
control
(spontaneous
histamine
release,
without
any
stimulus)
and
in
the
'total
histamine'
tubes,
respectively.
Since
supernatants
containing
amiloride
or
amiloride
derivatives
were
strongly
fluorescent,
we
used
a
radioimmunoassay
(Immunotech
S.A.,
Marseille-Luminy,
France)
to
measure
histamine
in
these
samples.
Statistical
analysis
Statistical
analysis
used
Student's
t-test
for
paired
variates.
P
<
0
05
was
considered
significant.
RESULTS
Experimental
conditions
for
IL-3
effect
In
preliminary
experiments,
optimal
conditions
for
IL-3
effect
on
anti-IgE-induced
histamine
release
were
defined.
In
non-
allergic
donors,
a
release
above
10%
of
total
histamine
content
in
the
presence
of
IL-3
alone
(100
pM)
was
observed
in
17%
of
the
donors
(n
=
77).
Leucocytes
from
these
donors
were
thus
not
used
for
the
present
study.
Maximal
increase
of
this
release
was
observed
at
10
and
100
pM
IL-3:
50-0+7-1%
and
47-7+3-6%,
respectively
versus
27
1
+
5
2%
in
the
presence
of
anti-IgE
alone
at
I
Mg/ml
(n
=
3;
mean
+
s.e.m.).
No
effect
was
observed
below
I
pM
IL-3.
When
IL-3
was
added
20
min
after
anti-IgE
at
optimal
concentration
(I
pg/ml)
for
20
min,
it
did
not
increase
the
anti-
IgE-induced
release:
61-6
+
5
1%
(P
<
0-05;
n
=4)
or
44-7
+
7
2%
(not
significant)
with
IL-3
added
before
or
after
anti-IgE,
respectively,
compared
with
42-6
+
4
6%
in
the
absence
of
IL-3.
However,
at
a
lower
anti-IgE
concentration
(0
1
pg/ml),
IL-3
was
still
able to
increase
the
release
of
histamine:
40
5
+
4.5%
(P<001)
or
37
5+5
3%
(P<0
05)
with
IL-3
added
before
or
after
anti-IgE,
respectively,
compared
with
17-7+4-5%
in
the
absence
of
IL-3.
With
anti-IgE
alone
at
0
01
pg/ml,
basophils
did
not
release
histamine,
but
when
primed
with
IL-3
(100
pM),
they
still
released
9-6+
3
9%
of
their
histamine
content
(P
<
0-05).
IL-3
decreases
the
external
Ca2+-dependence
of
IgE-mediated
histamine
release
Figure
1
shows
histamine
release
induced
by
anti-IgE
(1
ug/ml)
from
human
basophils
primed
or
not
by
IL-3
(100
pM),
at
defined
concentrations
of
external
Ca2+.
In
the
absence
of
IL-3,
as
expected,
no
release
was
observed
at
Ca2+
concentrations
below
100
pm.
Above
100
ym,
the
release
rapidly
increased
and
reached
34-0
+
8-6%
(n
=
5)
at
2
mm
Ca2
.
In
contrast,
in
the
presence
of
IL-3,
a
release
of
17-9+3-7%
was
observed
at
a
concentration
as
low
as
1
pm
Ca2+.
This
release
was,
however,
dependent
on
external
Ca2
,
since
it
was
abolished
(05
±
01%;
n
=
5)
in
the
presence
of
EGTA
(1
mM)
added
at
the
beginning
of
the
preincubation
period
with
IL-3.
At
Ca2+
concentrations
higher
than
1
pm,
the
release
progressively
increased
with
Ca2+
concentration,
in
parallel
with
the
release
without
IL-3,
to
reach
64-4+7-7%
at
2
mm
Ca2+.
Thus,
IL-3
induced
not
only
an
increase
of
IgE-mediated
histamine
release
at
a
fixed
Ca2+
concentration,
but
also
a
dramatic
decrease
of
the
Ca2+
concentration
necessary
for
this
release.
IL-3
effect
is
not
due
to
a
decrease
of
the
Na+
influx,
but
is
dependent
on
external
Na+
In
a
previous
study
we
showed
that
Na+
influx
strongly
inhibits
basophil
release
[13].
One
possibility
for
the
mechanism
of
the
IL-3
effect
on
basophils
was
that
this
cytokine
decreased
Na+
influx
and
consequently
increased
histamine
release.
Leucocytes
80
r
601-
Q)
a)
0
a,
.E
0
I
401-
20F
0
vAII
10
100
[Ca
2+0
(.LM)
1000
Fig.
1.
Effect
of
IL-3
on
external
Ca2+
requirement.
Leucocytes
were
preincubated
(5
min;
37°C)
with
IL-3
(0,
*)
or
diluting
buffer
alone
(0)
and
then
incubated
(30
min;
37°C)
with
anti-IgE
(1
pg/ml)
in
the
presence
of
defined
Ca2+
concentrations.
EGTA
(1
mM)
was
added
to
buffer
external
Ca2
+
(A).
Histamine
was
then
measured
in
the
supernatants
(n
=
5).
In
all
figures,
results
are
given
as
means
+
s.e.m.
of
net
per
cent
of
histamine
release
in
separate
experiments.
The
release
of
histamine
with
IL-3
alone
was
below
5%
and,
for
clarity,
is
not
shown
in
the
figure.
11105
-
I-
III
192

IL-3
effect
on
basophil
histamine
release
100
r
140
mM
Nao"
P<
0.05
801-
0
0X
0)
0)
0
Q)
a
60
f
40
201-
0
-IL-3
+IL-3
Low
Na'
NS
-IL-3
+IL-3
Fig.
2.
Role
of
Na+
ions
on
IL-3
effect.
Leucocytes
were
suspended
either
in
standard
saline
solution
(containing
140
mm
Na+)
or
in
low
Na+
solution
where
Na+
was
replaced
by
N-methyl-D-glucamine.
The
leucocyte
suspensions
were
preincubated
with
IL-3
(5
min)
or
buffer
alone
and
then
challenged
with
anti-IgE
(1
pg/ml)
or
buffer
alone.
Histamine
was
then
measured
in
supernatants
(n
=
4).
NS,
Not
signifi-
cant.
were
thus
suspended
in
low
Na+
medium
where
external
Na+
had
been
isosmotically
replaced
by
the
non-permeating
Na+
substitute
N-methyl-D-glucamine.
In
preliminary
experiments
we
observed
that
the
effect
of
IL-3
was
inhibited
in
low
Na+
100
_
80
-T
e~~~~~~~~~~
o
60
C
~~~~~~~~~~~T
.
40
-
U)
*
I
20-
0
10
100
No
/Ca2+
inhibitors
(sm)
Fig.
3.
Effect
of
inhibitors
of
Na+/Ca2+
exchanges
on
IL-3
effect.
Leucocytes
were
incubated
for
45
min
as
follows:
first,
anti-IgE
(0
1
Pig/
ml)
was
added
at
t
=
0;
second,
amiloride
(0)
or
benzamil
(-)
or
5-(N,N)-
dimethylamiloride
(A)
at
defined
concentrations
at
t
=
20
min;
third,
IL-
3
(100
pM)
at
t=25
min.
Histamine
was
then
measured
in
supernatants
(n
=
3).
The
release
of
histamine
with
IL-3
alone
or
inhibitors
of
Na+/
Ca2+
exchanges
alone
was
below
5%.
The
bar
indicates
the
release
of
histamine
with
anti-IgE
alone.
*P
<
0-05.
medium,
thus
suggesting
that
external
Na+
was
necessary
for
the
release
in
IL-3-primed
basophils
(data
not
shown).
How-
ever,
these
results
were
questionable.
Indeed,
the
effect
of
IL-3
was
determined
under
low
Na+
conditions,
thus
in
conditions
where
histamine
release
was
already
enhanced,
as
previously
shown
[13].
Therefore,
it
was
possible
that
the
absence
of
effect
of
IL-3
was
due
to
an
already
maximal
release
(due
to
low
Na+
medium)
that
IL-3
could
not
further
enhance.
To
answer
this
question,
new
investigations
were
performed
in
experimental
conditions
where
the
effect
of
Na+
removal
on
the
basal
anti-
IgE-induced
release
had
been
eliminated.
Indeed,
we
previously
observed
that
anti-IgE-induced
histamine
release
from
baso-
phils
of
a
group
of
atopic
subjects
was
not
increased
after
Na+
removal
[16].
Using
basophils
from
such
subjects,
we
observed
that
(i)
IL-3
increased
histamine
release
from
these
basophils
(from
42
5
+
8-6%
to
72-9
+
7-7%;
n
=
5)
and
(ii)
IL-3-increased
release
was
abolished
in
low
Na+
medium
(from
42-0
+
7-8%
to
44-6
+
5.6%)
(Fig.
2).
Similar
results
were
obtained
in
isotonic
HEPES-buffered
glucose
solution
and
at
lower
anti-IgE
concen-
trations
(data
not
shown).
Thus,
these
data
strongly
suggest
that
the
enhanced
histamine
release
in
IL-3-primed
basophils
is
not
due
to
a
down-modulation
of
the
inhibitory
effect
of
Na+
influx
which
we
previously
described
[13],
but
on
the
contrary,
that
external
Na+
is
necessary
for
IL-3
to
exert
its
effect.
Inhibition
of
the
IL-3
effect
by
amiloride
and
derivatives
The
reduction
of
the
external
Ca2+
dependence
and
the
external
Na+
dependence
were
evocative
of
Na+/Ca2+
exchanges.
Indeed,
it
could
be
suggested
that
Na+
influx
during
cell
activation
increased
cytosolic
Na+,
thus
allowing
exchanges
of
internal
Na+
and
external
Ca2+
which
finally
resulted
in
cytosolic
Ca2+
increase.
Therefore,
we
investigated
whether
amiloride,
an
inhibitor
of
the
Na+/Ca2+
and
Na4-/H+
exchanges,
was
able
to
inhibit
the
IL-3
effect.
In
preliminary
experiments,
amiloride
inhibited
the
release
from
basophils
both
primed
and
not
primed
by
IL-3.
Thus,
we
could
not
conclude
whether
amiloride
was
effective
on
the
IL-3
effect
itself.
We
then
took
advantage
of
the
results
reported
above
to
examine
the
influence
of
amiloride
on
the
effect
of
IL-3
after
the
release
induced
by
anti-IgE
(0-
I
ug/ml)
was
completed.
Under
these
conditions,
histamine
release
in
the
presence
of
anti-IgE
alone
was
39.5+773%
(n=
3),
and
reached
62-5
+444%
when
IL-3
was
added
at
the
end
of
the
incubation
period
with
anti-IgE
alone
(Fig.
3).
This
release
decreased,
but
not
significantly,
to
52-9
+
8-3
%
with
amiloride
100
pM.
With
benzamil,
an
amiloride
derivative
with
enhanced
specificity
for
Na+/Ca2+
exchanges
[17],
the
inhibitory
effect
was
more
marked
and
the
release
was
significantly
reduced
(41
9+3
9
%
and
43.9+4
0
%
with
benza-
mil
at
10
and
100
pm,
respectively)
to
near
the
basal
value
with
anti-IgE
alone.
By
contrast
5-(N,N-dimethyl)-amiloride,
a
more
specific
inhibitor
than
amiloride
of
Na+/H+
exchanges
[18],
did
not
inhibit
the
IL-3
effect
and
induced
a
slight,
but
not
significant,
increase
of
release
(Fig.
3).
DISCUSSION
The
aim
of
this
study
was
to
investigate
the
role
of
cations
in
the
potentiating
effect
of
IL-3
on
human
basophil
histamine
release.
The
salient
feature
of
the
present
data
was
the
dramatic
IL-3-
induced
decrease
in
the
external
Ca2+
requirement
for
histamine
193

194
F.
Beauvais
et
al.
release.
This
property
of
IL-3
was
previously
described
for
basophils
challenged
with
C5a
[11].
We
observed
that
anti-IgE-
induced
histamine
release
was
still
possible
with
IL-3-treated
basophils
in
the
presence
of
Ca2+
at
concentrations
as
low
as
I
rM.
However,
EGTA
in
the
external
medium
inhibited
the
IL-3
effect,
indicating
that
the
Ca2+
independence
of
histamine
release
induced
by
IL-3
was
only
partial.
The
presence
of
Na+
in
the
external
medium
was
necessary
to
observe
the
enhancing
effect
of
IL-3.
These
data
have
to
be
compared
with
our
previous
results,
which
indicated
on
the
contrary
that
removal
of
external
Na+
could
increase
histamine
release
induced
by
anti-IgE
alone
[13].
These
different
effects
of
external
Na+
most
probably
indicate
that
Na+
can
modulate
histamine
release
by
separate
mechanisms.
Taken
together,
the
dependence
on
external
Na+,
the
decrease
of
the
Ca2+
requirement-which
suggest
a
role
for
Na+/Ca2+
exchanges-and
a
possible
involvement
of
Na+
through
Na+/H+
exchanges,
prompted
us
to
examine
the
influence
of
amiloride,
an
Na+/H+
and
Na+/Ca2+
exchange
inhibitor,
and
its
derivatives
on
the
IL-3
effect.
Since
amiloride
inhibited
IgE-mediated
histamine
release
itself,
we
tested
ami-
loride
and
its
derivatives
on
the
IL-3
effect
after
anti-IgE-in
duced
histamine
release
was
terminated.
Indeed,
at
suboptimal
anti-IgE
concentration,
the
IL-3
effect
could
be
demonstrated
even
after
the
release
induced
by
anti-IgE
alone
reached
a
plateau.
The
inhibition
by
amiloride
and
benzamil
suggests
the
involvement
of
Na+/Ca2+
exchanges
in
IL-3-induced
potentia-
tion
of
IgE-mediated
histamine
release.
Na+-dependence,
lowering
of
the
external
Ca2+
requirement
and
inhibitory
effects
of
amiloride
and
derivatives-related
to
their
Na+/Ca2+
exchange
inhibitory
effects-suggest
a
role
for
Na+/Ca2+
exchanges
in
the
potentiating
effect
of
IL-3
on
IgE-
mediated
histamine
release.
Na+/Ca2+
exchanges
have
pre-
viously
been
shown
to
be
involved
in
IgE-mediated
exocytosis
from
rat
basophilic
leukaemia
cells,
allowing
a
sustained
Ca2+
plateau
[17].
In
our
model,
the
precise
step(s)
of
the
exocytosis
process
where
IL-3-mediated
Na+/Ca2+
exchanges
are
involved
remain(s)
to
be
determined.
However,
IL-3
has
many
effects
on
cells
involved
in
inflammation
and
allergy,
and
our
results
could
contribute
to
the
understanding
of
the
effect
of
IL-3
on
these
cells.
ACKNOWLEDGMENT
F.B.
was
supported
by
a
fellowship
from
Fondation
pour
la
Recherche
Medicale.
REFERENCES
I
Valent
P,
Schmidt
G,
Besemer
J
et
al.
Interleukin-3
is
a
differentia-
tion
factor
for
human
basophils.
Blood
1989;
73:1763-9.
2
Valent
P,
Besemer
J,
Muhm
M
et
al.
Interleukin
3
activates
human
blood
basophils
via
high-affinity
binding
sites.
Proc
Nati
Acad
Sci
USA
1989;
86:5542-6.
3
Bochner
BS,
McKelvey
AA,
Sterbinsky
SA
et
al.
IL-3
augments
adhesiveness
for
endothelium
and
CD
11
b
expression
in
human
basophils
but
not
neutrophils.
J
Immunol
1990;
145:1832-7.
4
Hirai
K,
Morita
Y,
Misaki
Y
et
al.
Modulation
of
human
basophil
histamine
release
by
hemopoietic
growth
factors.
J
Immunol
1988;
141:3958-64.
5
Alam
R,
Welter
JB,
Forsythe
PA
et
al.
Comparative
effect
of
recombinant
IL-
1,
-2,
-3,
-4
and
-6,
IFN-y,
granulocyte-macrophage-
colony-stimulating
factor
and
histamine-release
factors
on
the
secretion
of
histamine
from
basophils.
J
Immunol
1989;
142:3431-5.
6
Schleimer
RP,
Derse
CP,
Friedman
B
et
al.
Regulation
of
human
basophil
mediator
release
by
cytokines.
I.
Interaction
with
antiin-
flammatory
steroids.
J
Immunol
1989;
143:1310-7.
7
Kurimoto
Y,
De
Weck
AL,
Dahinden
CA.
The
effect
of
interleukin
3
upon
IgE-dependent
and
IgE-independent
basophil
degranulation
and
leukotriene
generation.
Eur
J
Immunol
1991;
21:361-8.
8
Bischoff
SC,
De
Weck
AL,
Dahinden
CA.
Interleukin
3
and
granulocyte/macrophage-colony-stimulating
factor
render
human
basophils
responsible
to
low
concentrations
of
complement
compo-
nent
C3a.
Proc
Natl
Acad
Sci
1990;
87:6813-7.
9
Dahinden
CA,
Kurimoto
Y,
De
Weck
AL
et
al.
The
neutrophil-
activating
peptide
NAF/NAP-l
induces
histamine
and
leukotriene
release
by
interleukin
3-primed
basophils.
J
Exp
Med
1989;
170:1787-92.
10
Brunner
T,
De
Weck
AL,
Dahinden
CA.
Platelet-activating
factor
induces
mediator
release
by
human
basophils
primed
with
IL-3,
granulocyte-macrophage
colony-stimulating
factor,
or
IL-5.
J
Immunol
1991;
147:237-42.
11
Kurimoto
Y,
De
Weck
AL,
Dahinden
CA.
Interleukin
3-dependent
mediator
release
in
basophils
triggered
by
C5a.
J
Exp
Med
1991;
170:467-79.
12
Krieger
M,
von
Tscharner
V,
Dahinden
CA.
Signal
transduction
for
interleukin-3-dependent
leukotriene
synthesis
in
normal
human
basophils:
opposing
role
of
tyrosine
kinase
and
protein
kinase
C.
Eur
J
Immunol
1992;
22:2907-13.
13
Beauvais
F,
Shimahara
T,
Inoue
I
et
al.
Regulation
of
human
basophil
activation.
II.
Histamine
release
is
potentiated
by
K+
efflux
and
inhibited
by
Na+
influx.
J
Immunol
1992;
148:149-54.
14
Grynkiewicz
G,
Poenie
M,
Tsien
RY.
A
new
generation
of
Ca2+
indicators
with
greatly
improved
fluorescence
properties.
J
Biol
Chem
1985;
260:3440-50.
15
Siraganian
RP,
Brodsky
MJ.
Automated
histamine
analysis
for
in
vitro
allergy
testing.
I.
A
method
utilizing
allergen-induced
hista-
mine
release
from
whole
blood.
J
Allergy
Clin
Immunol
1976;
57:525-39.
16
Beauvais
F,
Hi&blot
C,
Burtin
C
et
al.
Regulation
of
human
basophil
activation.
III.
Impairment
of
the
inhibitory
effect
of
Na+
on
IgE
mediated
histamine
release
in
patients
with
allergic
rhinitis.
J
Allergy
Clin
Immnol
1992;
90:52-8.
17
Stump
RF,
Oliver
JM,
Cragoe
EJ
Jr
et
al.
The
control
of
mediator
release
from
RBL-2H3
cells:
roles
for
Ca2
+,
Na
+,
and
protein
kinase
C.
J
Immunol
1987;
139:881-6.
18
Besterman
JM,
Tyrey
SJ,
Cragoe
EJ
Jr
et
al.
Inhibition
of
epidermal
growth
factor-induced
mitogenesis
by
amiloride
and
an
analog:
evidence
against
a
requirement
for
Na+/H+
exchange.
Proc
Natl
Acad
Sci
USA
1984;
81:6762-6.