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.
...to these alterations in CTMCs, MMC numbers were comparable between Mcpt5Cre/Dicerfl/fl mice and Dicerfl/fl control animals, as indicated by unchanged serum levels of mMCP-1 (Fig 1, H) and ...comparable expression of Mcpt1 and Mcpt2 mRNA in the small intestine in both groups (Fig 1, I and J). Because MCs are major effector cells of anaphylaxis, we next sought to investigate the response of Mcpt5Cre/Dicerfl/fl mice in IgE-mediated passive systemic anaphylaxis (Fig 1, K). In line with our findings, Dicer ablation in vivo has been shown to also affect maturation of granulocyte/macrophage progenitors toward neutrophils, macrophages, and dendritic cells, as well as T-cell differentiation, B-cell development, and germinal center formation.2,8 Expression of Mcpt5Cre has previously been demonstrated to be highly specific for CTMCs,4 with the exception of TH2 cell-mediated expansion of MMCs.9 To further assess the specificity of Mcpt5Cre-mediated deletion of Dicer, we next analyzed the number of different myeloid and lymphoid cells in peripheral blood, the spleen, and the peritoneal cavity (Fig 2).
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