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L//.),AS0 FII+ L-P;/(’%!1(’ 3,,’ !&&("-5 %* ,)( ,3 1$( /,*1 #,//,) #$",)%# /(’%#!& #,)’%1%,)* ,3 #$%&’$,,’M !33(#1%)- .6 1, FIJ ,3 1$( 6,6.&!1%,) ?,"&’?%’(+ H ‘(!#1%,)* 1$!1 !"( /(’%!1(’ 85 L-P !"( 156%#!&&5 "!6%’ ,)*(1M 6"(*()1%)- ?%1$ #&%)%#!& *5/61,/* ?%1$%) /%).1(* 1, ! 3(? $,."* !31(" (76,*."(+ F Q$( /,*1 3(!"(’ ,3 *5*1(/%# "(!#1%,)* %* !)!6$5&!7%*M ?$%#$ #!) 6",’.#( &%3(; 1$"(!1()%)- #!"’%,6.&/,)!"5 #,&&!6*(+ Q$( &%3(1%/( 6"(<!&()#( ,3 !)!6$5&!7%* %) 1$( 9)%1(’ C1!1(* %* (*1%/!1(’ 1, 8( 8(1?(() I+G;HJ R ?%1$ 6(!).1* !)’ 1"(( ).1* !##,.)1%)- 3," /!)5 ,3 1$(*( "(!#1%,)*+ L) 1("/* ,3 "%*: 3!#1,"*M 1$( /,*1 *%-)%3%#!)1 "%*: 3!#1," 3," ! 3!1!& !)!6$5&!#1%# (<()1 %* .)#,)1",&&(’ !*1$/!+ FF !"##$%& () *# *$,?(’ 1$!1 %) S.*1"!&%! 3",/ HIII; HIFOM NUJ ,3 1$( :),?) !)!6$5&!#1%# 3!1!&%1%(* @!11"%8.1!8&( 1, 3,,’ %)-(*1%,)D $!’ ! $%*1,"5 ,3 !*1$/!+ FF ‘(6"(*()1%)- ! ?(&&;(*1!8&%*$(’ 1(#$)%[.( TMG M 6"(#%*%,);#.1 &.)- *&%#(* @0ABCD 6",<%’( ! .)%[.( ,66,"1.)%15 1, &(!") !8,.1 1$( "(&!1%,)*$%6 8(1?(() !*1$/! !)’ 3,,’;!11"%8.1!8&( !)!6$5&!7%*+ 0ABC #,)1!%) !&& 1$( #(&&* ,3 1$( &,?(" "(*6%"!1,"5 1"!#1M %)#&.’%)- (6%1$(&%!& #(&&*M */,,1$ /.*#&( #(&&*M 3%8",8&!*1*M /!#",6$!-(*M !)’ /!*1 #(&&*+ T E",)#$,#,)*1"%#1%,) %* 6"%/!"%&5 /(’%!1(’ 85 /(’%!1,"* "(&(!*(’ 85 /!*1 #(&&* !)’ 8!*,6$%&*M %)#&.’%)- $%*1!/%)(M &(.:,1"%()(*M !)’ 6",*1!),%’*+ L#,)%#!&&5M $%*1!/%)( 8%)’* 1, 1$( dF "(#(61," ,) !%"?!5 */,,1$ /.*#&( #(&&* !)’ %)’.#(* !) !&&("-();*6(#%3%# %//(’%!1( !%"?!5 #,)*1"%#1%,) ’(3%)(’ !* 1$( (!"&5 !%"?!5 "(*6,)*(+ T ‘(#()1&5M W(&-!’, (1 !&+ *$,?(’ 1$!1 6!**%<( *()*%1%>!1%,) 1, ’.*1 /%1( %) 0ABC 3",/ ’,),"* ?%1$ $%*1,"5 ,3 #!)#(" #!.*(’ 8",)#$,#,)*1"%#1%,) !31(" 1, 1$( ’.*1 /%1( !&&("-()+ T =( [.(*1%,)(’ ?$(1$(" !%"?!5* %) 0ABC 3",/ ! 3,,’;!&&("-%# @^SD ’,)," ?%1$ :),?) 6,*%1%<( *("./ *6(#%3%# L-P !)’ ! $%*1,"5 ,3 !*1$/! ?,.&’ "(*6,)’ 1, 3,,’ !&&("-()* 1, ?$%#$ 1$(5 ?("( *()*%1%>(’ ?%1$ 8",)#$,#,)*1"%#1%,) 6,*1;/,"1(/+ E!*(’ ,) 1$( &%1("!1."(M ?( $56,1$(*%>(’ 1$!1 1$("( ?,.&’ 8( /!":(’ 8",)#$%!& #,)*1"%#1%,) %) 0ABC *()*%1%>(’ ?%1$ 6(!).1 !)’ #!*$(? %) 0ABC 3",/ ! ’,)," ?%1$ $%*1,"5 ,3 3!1!& !)!6$5&!7%* 1, #!*$(?+ Food-Allergic (FA) Donor (hl237) Non Food-Allergic Donor (Control) (hl238) Age 11 years 20 years Race/Sex H / F B / M Height/Weight/BMI 60’’ / 42 kg / 18.1 72’’ / 82 kg / 24.5 Past Medical History Food allergy, Asthma None Medications Unspecified inhaler None Cause of Death Anaphylaxis (presumed Cashew) Head Trauma 6$?.3( H) C(3.D 4?@ 03%--7’$&I$&? >$#+ #+( 60!!4 3(0(9#%3 %& D"-# 0(’’- ’(",- #% ,(?3"&.’"#$%& "&, -(03(#$%& %5 93(5%3D(, D(,$"#%3- #+"# ’(", #% 23%&0+$"’ 3("0#$J$#: "5#(3 $&?(-#$%& %5 5%%, "’’(3?(&G 0,*1;*5*1(/%# ’(-"!).&!1%,) &(!’* 1, ’,?) "(-.&!1(’ 6!1$?!5 !#1%<!1%,) <%! C5:;/(’%!1(’ *%-)!&%)-M #!.*%)- !)("-5+ Food-Allergic (FA) Donor Concentration (kUA/I) Non Food-Allergic (Control) Donor Concentration (kUA/I) f2 (Milk) 2.21 0.11 f13 (Peanut) 11.7 0.21 f20 (Almond) 0.13 <0.10 f201 (Pecan) <0.10 <0.10 f202 (Cashew) 4.13 <0.10 f245 (Egg) 0.63 <0.10 f422 (Peanut r Ara h1) 0.12 <0.10 f423 (Peanut r Ara h2) 10.8 <0.10 f424 (Peanut r Ara h3) <0.10 <0.10 !(-.’#- Bronchial Constriction Vasodilation Pruritus (Visceral Hypersensitivity) Urticaria Histamine- induced: Mast cell degranulation of histamine (among other preformed mediators) FcεRI Allergen- specific IgE FcεRI IgE cross- linking Allergen ITAM ITAM ITAM ITAM Syk + Lyn + Phosphorylation Allergen Dampened activation of mast cell degranulation upon subsequent exposure to allergen FcεRI Allergen- specific IgE Allergen FcεRI IgE cross- linking Allergen ITAM ITAM ITAM ITAM Syk Cbl - MAST CELL Syk SHP - - Down-regulation of Syk 6$?.3( K) 1$3>": !(-9%&-$J(&(-- #% 6%%, "’’(3?(&- $& A/BC 53%D " 61 ,%&%3G ^S ’,)," *$,?(’ ), !%"?!5* "(*6,)*%<()(** 1, #!*$(? @SD 8.1 $!’ ! *%-)%3%#!)1 "(*6,)*( 1, 6(!).1 !1 !&& 1%/( 6,%)1*@ED @"(6"(*()1!1%<( 6$,1,/%#",-"!6$*D+ @AD @WD A,)1",& ’,)," ’%’ ),1 *$,? "(*6,)*%<()(** 1, (%1$(" 3,,’ !&&("-()+ 6$?.3( L) *("& "$3>":- 3(-9%&-$J(&(-- #% 5%%, "’’(3?(&- $& A/BC 53%D 61 ,%&%3G S%"?!5* *%-)%3%#!)1&5 #,)1"!#1(’ 1, 6(!).1 @‘(’D @)oUD @6pI+IGD 8.1 ),1 1, #!*$(? @E&.(D @)oUD !1 HIM NIM !)’ ONI /%).1(* 6,*1 (76,*."(+ Q$%* 3%)’%)- ,##.""(’ ’(*6%1( $%*1,"5 ,3 3!1!& !)!6$5&!7%* 1, #!*$(? !)’ 6,*%1%<( *("./ L-P 1, #!*$(?; &%:(&5 "(6"(*()1%)- !)("-5 1, 1$%* !&&("-()+ M"2’( 4G E(D%?3"9+$0-G M"2’( 44G 1’’(3?(& C9(0$5$0 4?@ M(-#$&?G 6$?.3( N) *("& "$3>":- 3(-9%&-$J(&(-- #% 5%%, "’’(3?(&- $& A/BC 53%D 0%%’ O&%&7"’’(3?$0P ,%&%3G S%"?!5* ’%’ ),1 "(*6,)’ 1, (%1$(" 6(!).1 @‘(’D @)oFHD ," #!*$(? @)oFHD #,/6!"(’ 1, 8!*!& /(!*."(*+ Q$%* 3%)’%)- ,##.""(’ ’(*6%1( (<%’()#( 1$!1 1$( !%"?!5* ?("( #,)1"!#1%&( @#!"8!#$,& "(*6,)*%<(D+ Basal Histamine Forskolin 20 minutes 60 minutes 360 minutes 0 20 40 60 80 100 Treatments and Times % contraction Cashew (n=8) Peanut (n=8) * ** *** Basal Carbachol Forskolin 20 minutes 60 minutes 360 minutes 0 20 40 60 80 100 % contraction Cashew (n=12) Peanut (n=12) Treatments and Times 6.&,$&?) Q$%* ?,": ?!* 3.)’(’ 85 kLd kLSLW @FgIUSLFHFOTG;IFSFDM kLd kASQC @gBHQ‘IIIINOM 9BFQ‘IIIIOZDM kLd kLj]C @0HIj]FHFHZODM S":!)*!* E%,*#%()#(* L)*1%1.1(M ]!"%,) E B5,) k(? C#%()1%*1 W(<(&,6/()1 S?!"’M !)’ 9S]C A&%)%#%!) C#%()1%*1 0",-"!/+ E W S A E W ^Cg ESCSB dLC OI/%) NI/%) ONI/%) =(&& ST $BHOR @^SD ^Cg ESCSB dLC =(&& ER $BHOR @^SD OI/%) NI/%) ONI/%) F/-K/B A!*$(? (71"!#1 F/-K/B 0(!).1 (71"!#1 =(&& SF $BHOU @A,)1",&D =(&& AU $BHOU @A,)1",&D F/-K/B A!*$(? (71"!#1 F/-K/B 0(!).1 (71"!#1 ^Cg ESCSB AA$ OI/%) NI/%) ONI/%) OI/%) NI/%) ONI/%) ^Cg ESCSB AA$ 1 Q / E MAST CELL
Transcript of 6%%,74&,.0(,81&9+:’;$-)88:8/% #$’$#:8 ......
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Food-Allergic (FA) Donor (hl237) Non Food-Allergic Donor (Control) (hl238)
Age 11 years 20 years
Race/Sex H / F B / M
Height/Weight/BMI 60’’ / 42 kg / 18.1 72’’ / 82 kg / 24.5
Past Medical History Food allergy, Asthma None
Medications Unspecified inhaler None
Cause of Death Anaphylaxis (presumed Cashew) Head Trauma
6$?.3( H) C(3.D84?@803%--7'$&I$&?8>$#+8#+(860!!4 3(0(9#%38%&8D"-#80(''-8'(",-
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3("0#$J$#:8"5#(38$&?(-#$%&8%585%%,8"''(3?(&G80,*1;*5*1(/%#2'(-"!).&!1%,)2&(!'*21,2
',?)2"(-.&!1('26!1$?!52!#1%<!1%,)2<%!2C5:;/('%!1(' *%-)!&%)-M2#!.*%)-2!)("-5+
Food-Allergic (FA) Donor Concentration
(kUA/I)
Non Food-Allergic (Control) Donor
Concentration (kUA/I)
f2 (Milk) 2.21 0.11
f13 (Peanut) 11.7 0.21
f20 (Almond) 0.13 <0.10
f201 (Pecan) <0.10 <0.10
f202 (Cashew) 4.13 <0.10
f245 (Egg) 0.63 <0.10
f422 (Peanut r Ara h1) 0.12 <0.10
f423 (Peanut r Ara h2) 10.8 <0.10
f424 (Peanut r Ara h3) <0.10 <0.10
!(-.'#-
Bronchial
Constriction
Vasodilation
Pruritus (Visceral
Hypersensitivity)
Urticaria
Histamine-
induced:
Mast cell degranulation of
histamine (among other
preformed mediators)
FcεRI
Allergen-
specific IgE
FcεRI
IgE
cross-
linking
Allergen
ITAMITAM ITAMITAMSyk
+
Lyn
+Phosphorylation
Allergen
Dampened activation of
mast cell degranulation
upon subsequent exposure
to allergen
FcεRI
Allergen-
specific IgE
Allergen
FcεRI
IgE
cross-
linking
Allergen
ITAMITAM ITAMITAM
SykCbl
-M A S T C E L L
SykSHP
- -Down-regulation of
Syk
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Ba
sa
l
His
tam
ine
Fo
rsk
oli
n
20
min
ute
s
60
min
ute
s
36
0 m
inu
tes
0
20
40
60
80
100
Treatments and Times
% c
on
tracti
on
Cashew (n=8)
Peanut (n=8)
*
**
***
Ba
sa
l
Ca
rba
ch
ol
Fo
rsk
oli
n
20
min
ute
s
60
min
ute
s
36
0 m
inu
tes
0
20
40
60
80
100
% c
on
tracti
on
Cashew (n=12)
Peanut (n=12)
Treatments and Times
6.&,$&?)88Q$%*2?,":2?!*23.)'('2852kLd2kLSLW2@FgIUSLFHFOTG;IFSFDM2kLd2kASQC2@gBHQ`IIIINOM29BFQ`IIIIOZDM2kLd2kLj]C2
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1
Q
/
E
M A S T C E L L
