title: Selective ablation of mast cells or basophils reduces peanut-induced anaphylaxis in mice.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Laurent L
authors.initials: LL
authors.lastname: Reber
authors.forename: Thomas
authors.initials: T
authors.lastname: Marichal
authors.forename: Kaori
authors.initials: K
authors.lastname: Mukai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kita
authors.forename: Suzumi M
authors.initials: SM
authors.lastname: Tokuoka
authors.forename: Axel
authors.initials: A
authors.lastname: Roers
authors.forename: Karin
authors.initials: K
authors.lastname: Hartmann
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
authors.forename: Kari C
authors.initials: KC
authors.lastname: Nadeau
authors.forename: Mindy
authors.initials: M
authors.lastname: Tsai
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Galli
mesh_terms: D000707:Anaphylaxis / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D010367:Arachis / Q000276:immunology*; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D004167:Diphtheria Toxin / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D021183:Peanut Hypersensitivity / Q000150:complications* / Q000276:immunology* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D004167:Diphtheria Toxin; D019009:Proto-Oncogene Proteins c-kit
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
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