Intestinal mast cell levels control severity of oral antigen-induced anaphylaxis in mice.
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.
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Richard
R
Ahrens
Heather
H
Osterfeld
David
D
Wu
Chun-Yu
CY
Chen
Muthuvel
M
Arumugam
Katherine
K
Groschwitz
Richard
R
Strait
Yui-Hsi
YH
Wang
Fred D
FD
Finkelman
Simon P
SP
Hogan
D000284:Administration, Oral; D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D002199:Capillary Permeability / Q000276:immunology; D002452:Cell Count; D015194:Diffusion Chambers, Culture; D004195:Disease Models, Animal; D005512:Food Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007583:Jejunum / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology; D012720:Severity of Illness Index
D000941:Antigens; D017455:Receptors, IgE; D007073:Immunoglobulin E; D010047:Ovalbumin