Intestinal mast cell levels control severity of oral antigen-induced anaphylaxis in mice

Am J Pathol. 2012 Apr;180(4):1535-46. doi: 10.1016/j.ajpath.2011.12.036. Epub 2012 Feb 7.

Abstract

Food-triggered anaphylaxis can encompass a variety of symptoms that affect multiple organ systems and can be life threatening. The molecular distinction between non-life-threatening and life-threatening modes of such anaphylaxis has not yet been delineated. In this study, we sought to identify the specific immune functions that regulate the severity of oral antigen-induced anaphylaxis. We thus developed an experimental mouse model in which repeated oral challenge of ovalbumin-primed mice induced an FcεRI- and IgE-dependent oral antigen-triggered anaphylaxis that involved multiple organ systems. Strikingly, the severity of the systemic symptoms of anaphylaxis (eg, hypothermia) positively correlated with the levels of intestinal mast cells (r = -0.53; P < 0.009). In addition, transgenic mice with both increased intestinal and normal systemic levels of mast cells showed increased severity of both intestinal and extra-intestinal symptoms of IgE-mediated passive as well as oral antigen- and IgE-triggered anaphylaxis. In conclusion, these observations indicate that the density of intestinal mast cells controls the severity of oral antigen-induced anaphylaxis. Thus, an awareness of intestinal mast cell levels in patients with food allergies may aid in determining their susceptibility to life-threatening anaphylaxis and may eventually aid in the treatment of food-triggered anaphylaxis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Anaphylaxis / immunology*
  • Animals
  • Antigens / administration & dosage*
  • Antigens / immunology
  • Capillary Permeability / immunology
  • Cell Count
  • Diffusion Chambers, Culture
  • Disease Models, Animal
  • Food Hypersensitivity / immunology
  • Immunoglobulin E / immunology
  • Jejunum / immunology*
  • Mast Cells / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Receptors, IgE / immunology
  • Severity of Illness Index

Substances

  • Antigens
  • Receptors, IgE
  • Immunoglobulin E
  • Ovalbumin