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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:132

Article

Reber, Laurent L.¹  Marichal, Thomas¹  Mukai, Kaori¹  Kita, Yoshihiro⁴  Tokuoka, Suzumi M.⁴  Roers, Axel⁵  Hartmann, Karin⁶  Karasuyama, Hajime⁷  Nadeau, Kari C.²  Tsai, Mindy¹  Galli, Stephen J.^1,3 

[1] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Div Immunol & Allergy, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA

[4] Univ Tokyo, Fac Med, Dept Lipid, Tokyo 1138654, Japan

[5] Tech Univ Dresden, Med Fac Carl Gustav Carus, Inst Immunol, Dresden, Germany

[6] Univ Cologne, Dept Dermatol, Cologne, Germany

[7] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, CREST, Dept Immune Regulat,JST, Tokyo, Japan

关键词: Peanut;    allergy;    neutrophils;    diphtheria toxin;    Kit(W-sh/W-sh);    mast cells;    anaphylaxis;    basophils;    carboxypeptidase A3;    mast cell protease 5;   

DOI  :  10.1016/j.jaci.2013.06.008

来源: Elsevier

【 摘 要 】

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.

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