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

Abstract

Background Studies using 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 using such approaches is complicated because c-kit mutant mice have several phenotypic abnormalities in addition to MC deficiency and 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 (WT) 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 KitW-sh/W-sh mice developed reduced immediate hypothermia, as well as a late phase drop 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 Mcpt8DTR mice, respectively, and treatment of WT mice with the basophil-depleting antibody Ba103, significantly reduced peanut-induced hypothermia. Non-c-kit mutant MC- and basophil-deficient Cpa3-Cre; Mcl-1fl/fl mice developed 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 KitW-sh/W-sh mice may influence the responses of these mice in this PIA model.

IgE and Mast Cells

“…In other models of murine food allergy, anaphylaxis can be evoked following parenteral injection of allergen, a nonphysiologic means of allergen exposure. In this setting, cells other than mast cells and molecules other than IgE have been shown to contribute to the severity of the anaphylaxis (Oettgen et al, 1994;Khodoun et al, 2009;Reber et al, 2013). In our ingestion challenge model, however, both anaphylaxis and other measures of mast cell activation are abrogated in the absence of IgE or FcεRI Mathias et al, 2011).…”

“…Disruption of the skin barrier as occurs in atopic dermatitis, a condition associated with a high risk of food allergy in infants, leads to the development of anaphylactic food allergy in mouse models (Bartnikas et al, 2013). Together, these models have established clear requirements for IgE and mast cells in the acute allergic responses to food allergens (Bartnikas et al, 2013;Brandt et al, 2003;Reber et al, 2013).…”

Analyzing the Functions of Mast Cells <em>In Vivo</em> Using '<em>Mast Cell Knock-in</em>' Mice

“…I.v. transfer of BMCMCs also results in high levels of MCs in the spleen, whereas very few native MCs are typically found in this organ in wild type mice 23,56 . Importantly, previous reports demonstrated that i.v.…”

Ablation of a small subpopulation of diabetes-specific bone marrow-derived cells in mice protects against diabetic neuropathy

“…We took advantage of the DT ablation strategy (3) by generating transgenic mice with insulin promoter-driven DT receptor (DTR) expression to confer hyperglycemia-dependent DTR expression in these mice. The analogous strategy had previously been used successfully to selectively ablate B cells (5), dendritic cells (13), mast cells (7,15), and macrophages (10) in mice. Because we used the insulin promoter for creating the DTR mice, we had to circumvent the production of DTR by pancreatic ␤-cell by using these mice as BMT donors.…”