title: Novel basophil- or eosinophil-depleted mouse models for functional analyses of allergic inflammation.
abstract: Basophils and eosinophils play important roles in various host defense mechanisms but also act as harmful effectors in allergic disorders. We generated novel basophil- and eosinophil-depletion mouse models by introducing the human diphtheria toxin (DT) receptor gene under the control of the mouse CD203c and the eosinophil peroxidase promoter, respectively, to study the critical roles of these cells in the immunological response. These mice exhibited selective depletion of the target cells upon DT administration. In the basophil-depletion model, DT administration attenuated a drop in body temperature in IgG-mediated systemic anaphylaxis in a dose-dependent manner and almost completely abolished the development of ear swelling in IgE-mediated chronic allergic inflammation (IgE-CAI), a typical skin swelling reaction with massive eosinophil infiltration. In contrast, in the eosinophil-depletion model, DT administration ameliorated the ear swelling in IgE-CAI whether DT was administered before, simultaneously, or after, antigen challenge, with significantly lower numbers of eosinophils infiltrating into the swelling site. These results confirm that basophils and eosinophils act as the initiator and the effector, respectively, in IgE-CAI. In addition, antibody array analysis suggested that eotaxin-2 is a principal chemokine that attracts proinflammatory cells, leading to chronic allergic inflammation. Thus, the two mouse models established in this study are potentially useful and powerful tools for studying the in vivo roles of basophils and eosinophils. The combination of basophil- and eosinophil-depletion mouse models provides a new approach to understanding the complicated mechanism of allergic inflammation in conditions such as atopic dermatitis and asthma.
authors.affiliation: Mammalian Genetics Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. matsuoka-kn@igakuken.or.jp
authors.forename: Kunie
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shitara
authors.forename: Choji
authors.initials: C
authors.lastname: Taya
authors.forename: Kenji
authors.initials: K
authors.lastname: Kohno
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kikkawa
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yonekawa
mesh_terms: D000818:Animals; D001491:Basophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D004167:Diphtheria Toxin / Q000633:toxicity; D004195:Disease Models, Animal; D004423:Ear / Q000473:pathology; D047209:Eosinophil Peroxidase / Q000235:genetics; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010727:Phosphoric Diester Hydrolases / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D004167:Diphtheria Toxin; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D007073:Immunoglobulin E; D047209:Eosinophil Peroxidase; D010727:Phosphoric Diester Hydrolases