Food, drug, insect sting allergy, and anaphylaxisSelective ablation of mast cells or basophils reduces peanut-induced anaphylaxis in mice
Section snippets
Mice
C57BL/6J mice and iDTR mice (C57BL/6-Gt[ROSA]26Sortm1(HBEGF)Awai/J) were purchased from Jackson Laboratories (Bar Harbor, Me). C57BL/6-KitW-sh/W-sh mice were originally provided by Peter Besmer (Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY); we then backcrossed these mice to C57BL/6J mice for more than 11 generations.29 Mcpt8DTR mice,39 Mcpt5-Cre mice,31, 34 and Cpa3-Cre;Mcl-1fl/fl mice (and the corresponding control Cpa3-Cre;Mcl-1+/+ mice)33 on the C57BL/6
PIA in c-kit mutant MC-deficient mice
We first assessed the response of c-kit mutant MC-deficient C57BL/6J-KitW-sh/W-sh (KitW-sh/W-sh) mice in this PIA model. Peanut-sensitized WT and KitW-sh/W-sh mice exhibited similar levels of peanut-specific IgE and IgG1 antibodies in the serum (see Fig E1 in this article's Online Repository at www.jacionline.org). KitW-sh/W-sh mice had reduced (although still significant) hypothermia compared with WT mice during the first hour after peanut challenge, and none of the mice died (3/18 WT mice
Discussion
Several studies using c-kit mutant KitW/W-v and KitW-sh/W-sh MC-deficient mice have suggested that MCs can significantly contribute to PIA.21, 22, 40 In this report we confirmed these findings by showing that KitW-sh/W-sh mice had reduced immediate hypothermia in this PIA model. However, we found that KitW-sh/W-sh mice also exhibited a previously unreported late decrease in body temperature that occurred between 3 and 6 hours after peanut challenge and after the hypothermia induced acutely by
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L.L.R. is the recipient of fellowships from the French “Fondation pour la Recherche Médicale FRM” and the Stanford Pediatric Research Fund of the Lucile Packard Foundation for Children’s Health and the Stanford CTSA (National Institutes of Health grant UL1 RR025744). T.M. is supported by a fellowship from the Belgium American Educational Foundation and a Marie Curie International outgoing Fellowship for Career Development: 299954. K.H. acknowledges support from the German Research Council (DFG; CRC/SFB832, project A14). S.J.G. acknowledges support from National Institutes of Health grants AI023990, CA072074, and AI070813.