title: Chronic inflammation of the skin can be induced in IgE transgenic mice by means of a single challenge of multivalent antigen.
abstract: BACKGROUND
  It is now widely accepted that IgE mediates immediate-type allergic response. However, the pathologic role of IgE is controversial in the chronic allergic inflammation observed in atopic diseases, such as asthma and atopic dermatitis.
  
  
  OBJECTIVE
  We investigated the role of IgE in cutaneous allergic reactions by using 2 newly developed lines of antigen-specific IgE transgenic mice.
  
  
  METHODS
  IgE transgenic mice were administered subcutaneously with corresponding antigens, and the subsequent ear swelling was measured.
  
  
  RESULTS
  A single subcutaneous administration of TNP-conjugated ovalbumin (OVA) into the ears of nonimmunized mice carrying the TNP-specific IgE transgene elicited immediate-phase and late-phase ear swelling as expected, which peaked at 20 minutes and 8 hours later, respectively. Interestingly, however, 2 to 3 days after the antigen challenge, more intense ear swelling appeared. Its magnitude and duration were dependent on the valency of TNP in OVA, as well as the dose of TNP-OVA, and it lasted over 1 month when 100 microg of OVA conjugated with 11 molecules of TNP was given. Interestingly, administration of OVA to OVA-specific IgE transgenic mice elicited immediate-phase and late-phase ear swelling but not third-phase ear swelling. Massive infiltration of inflammatory cells was observed in the third-phase ear swelling of TNP-specific IgE transgenic mice. Cyclosporine A almost completely inhibited the third-phase ear swelling and cellular infiltration, whereas an antihistamine, cyproheptadine, did not show any significant effect on the third-phase reaction.
  
  
  CONCLUSIONS
  These results indicate that IgE can trigger not only immediate-type hypersensitivity but also chronic allergic inflammation. Our findings highlight a novel immunopathologic role of IgE in chronic atopic disorders.
authors.affiliation: Research Laboratories, Sankyo Co, Ltd, Tokyo, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Sato
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hirahara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yoshitomi
authors.forename: Takachika
authors.initials: T
authors.lastname: Azuma
authors.forename: Kunie
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kubo
authors.forename: Choji
authors.initials: C
authors.lastname: Taya
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yonekawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
authors.forename: Akio
authors.initials: A
authors.lastname: Shiraishi
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D003872:Dermatitis / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004423:Ear; D004487:Edema / Q000276:immunology; D000939:Epitopes; D006241:Haptens / Q000008:administration & dosage; D007073:Immunoglobulin E / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology*; D010851:Picrates / Q000276:immunology
chemical_list: D000941:Antigens; D000939:Epitopes; D006241:Haptens; D010851:Picrates; D007073:Immunoglobulin E; C005858:picric acid