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J Allergy Clin Immunol. 2013 Oct;132(4):881-8.e1-11. doi: 10.1016/j.jaci.2013.06.008. Epub 2013 Aug 1.

Selective ablation of mast cells or basophils reduces peanut-induced anaphylaxis in mice.

Author information

1
Department of Pathology, Stanford University School of Medicine, Stanford, Calif.

Abstract

BACKGROUND:

Studies with c-kit mutant mast cell (MC)-deficient mice and antibody-mediated depletion of basophils suggest that both MCs and basophils can contribute to peanut-induced anaphylaxis (PIA). However, interpretation of data obtained by using such approaches is complicated because c-kit mutant mice have several phenotypic abnormalities in addition to MC deficiency and because basophil-depleting antibodies can also react with MCs.

OBJECTIVE:

We analyzed (1) the changes in the features of PIA in mice after the selective and inducible ablation of MCs or basophils and (2) the possible importance of effector cells other than MCs and basophils in the PIA response.

METHODS:

Wild-type and various mutant mice were orally sensitized with peanut extract and cholera toxin weekly for 4 weeks and challenged intraperitoneally with peanut extract 2 weeks later.

RESULTS:

Peanut-challenged, MC-deficient Kit(W-sh/W-sh) mice had reduced immediate hypothermia, as well as a late-phase decrease in body temperature that was abrogated by antibody-mediated depletion of neutrophils. Diphtheria toxin-mediated selective depletion of MCs or basophils in Mcpt5-Cre;iDTR and Mcpt8(DTR) mice, respectively, and treatment of wild-type mice with the basophil-depleting antibody Ba103 significantly reduced peanut-induced hypothermia. Non-c-kit mutant MC- and basophil-deficient Cpa3-Cre;Mcl-1(fl/fl) mice had reduced but still significant responses to peanut.

CONCLUSION:

Inducible and selective ablation of MCs or basophils in non-c-kit mutant mice can significantly reduce PIA, but partial responses to peanut can still be observed in the virtual absence of both cell types. The neutrophilia in Kit(W-sh/W-sh) mice might influence the responses of these mice in this PIA model.

KEYWORDS:

BMCMC; Bone marrow–derived cultured mast cell; CTMC; Carboxypeptidase A3; Connective tissue–type mast cells; Cpa3; DT; DTR; Diphtheria toxin; Diphtheria toxin receptor; Kit(W-sh/W-sh); MC; MMC; Mast cell; Mast cell protease; Mcpt; Mucosal mast cell; PAF; PIA; PSA; Passive systemic anaphylaxis; Peanut; Peanut-induced anaphylaxis; Platelet-activating factor; WT; Wild-type; allergy; anaphylaxis; basophils; carboxypeptidase A3; diphtheria toxin; mast cell protease 5; mast cells; neutrophils

PMID:
23915716
PMCID:
PMC3794715
DOI:
10.1016/j.jaci.2013.06.008
[Indexed for MEDLINE]
Free PMC Article
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