A new, rapid in vivo method to evaluate allergic responses through distinctive distribution of a fluorescent-labeled immune complex: Potential to investigate anti-allergic effects of compounds administered either systemically or topically to the skin

J Immunol Methods. 2016 Jan:428:58-68. doi: 10.1016/j.jim.2015.11.010. Epub 2015 Nov 28.

Abstract

We herein established a new method to evaluate allergic responses in mice rapidly and easily with ethical improvement by reducing the number of animals used. A single intravenous injection of a mixture of anti-OVA monoclonal IgE and fluorescein-ovalbumin (FITC-OVA) induced the distinctive spotted distribution of FITC-OVA in skin, named "ASDIS (Anaphylaxis-dependent Spotted Distribution of a fluorescent-labeled Immune complex in Skin)", and this was easily detected by in vivo imaging. The parallel induction of hypothermia, scratching, serum histamine increases, and ASDIS as well as the inhibition of ASDIS by either the systemic administration of a histamine H1 receptor antagonist or mast cell-depleting antibody suggested that our method, which only required 15 min, induced these allergic responses including ASDIS. Relatively mild but significant ASDIS was induced also in mice with passive systemic anaphylaxis by the method, requiring 2 separate days. The painting of anti-histamines on the skin markedly reduced ASDIS in the painted area only, suggesting the potential of this model to simultaneously compare the anti-allergic effects of several candidate compounds with control drugs in the same mice. ASDIS was suggested to originate from extravasated FITC-OVA/OE-1 immune complexes from blood to skin tissues other than mast cells. Our new method has the advantages of rapidity, easy method, and lower animal numbers to evaluate anti-allergic compounds as well as the characteristics of the used antibody, antigen, labeling molecules, additives, and other formulations. Our model for inducing ASDIS may contribute to the development of anti-allergic drugs, especially those intended for application to the skin.

Keywords: Allergy; In vivo imaging; Monoclonal IgE; New allergic model; Ovalbumin; Skin.

Publication types

  • Evaluation Study

MeSH terms

  • Administration, Topical
  • Allergens / administration & dosage
  • Allergens / immunology*
  • Anaphylaxis / drug therapy*
  • Anaphylaxis / immunology
  • Animals
  • Anti-Allergic Agents / administration & dosage*
  • Anti-Allergic Agents / pharmacology*
  • Anti-Allergic Agents / therapeutic use
  • Antigen-Antibody Complex / analysis*
  • Antigen-Antibody Complex / immunology
  • Fluorescence
  • Immunoglobulin E / administration & dosage
  • Immunoglobulin E / immunology
  • Injections, Intravenous
  • Mice
  • Mice, Hairless
  • Mice, Inbred DBA
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology*
  • Skin / drug effects*
  • Skin / immunology

Substances

  • Allergens
  • Anti-Allergic Agents
  • Antigen-Antibody Complex
  • fluorescein-ovalbumin
  • Immunoglobulin E
  • Ovalbumin