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Epicutaneous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis - PubMed

Epicutaneous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis

Lisa M Bartnikas et al. J Allergy Clin Immunol. 2013 Feb.

Abstract

Background: Sensitization to food antigen can occur through cutaneous exposure.

Objective: We sought to test the hypothesis that epicutaneous sensitization with food antigen predisposes to IgE-mediated anaphylaxis on oral allergen challenge.

Methods: BALB/c mice were epicutaneously sensitized by repeated application of ovalbumin (OVA) to tape-stripped skin over 7 weeks or orally immunized with OVA and cholera toxin (CT) weekly for 8 weeks and then orally challenged with OVA. Body temperature was monitored, and serum mouse mast cell protease 1 levels were determined after challenge. Tissue mast cell (MC) counts were examined by using chloroacetate esterase staining. Levels of serum OVA-specific IgE and IgG(1) antibodies and cytokines in supernatants of OVA-stimulated splenocytes were measured by means of ELISA. Serum IL-4 levels were measured by using an in vivo cytokine capture assay.

Results: Epicutaneously sensitized mice exhibited expansion of connective tissue MCs in the jejunum, increased serum IL-4 levels, and systemic anaphylaxis after oral challenge, as evidenced by decreased body temperature and increased serum mouse mast cell protease 1 levels. Intestinal MC expansion and anaphylaxis were IgE dependent because they did not occur in epicutaneously sensitized IgE(-/-) mice. Mice orally immunized with OVA plus CT did not have increased serum IL-4 levels, expanded intestinal MCs, or anaphylaxis after oral challenge, despite OVA-specific IgE levels and splenocyte cytokine production in response to OVA stimulation, which were comparable with those of epicutaneously sensitized mice.

Conclusion: Epicutaneously sensitized mice, but not mice orally immunized with antigen plus CT, have expansion of intestinal MCs and IgE-mediated anaphylaxis after single oral antigen challenge. IgE is necessary but not sufficient for food anaphylaxis, and MC expansion in the gut can play an important role in the development of anaphylaxis.

Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

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Figures

Figure 1
Figure 1. EC sensitization with OVA results in anaphylaxis following oral OVA challenge

A. Experimental protocol. B. OVA specific IgE and IgG1 levels. C. Core body temperature after challenge. D. Serum mMCP-1 levels pre and 60 min post challenge. n=8–20 mice/group. Columns and bars represent mean and SEM. * P <0.05, *** P <0.001. ns = not significant.

Figure 2
Figure 2. Anaphylaxis following oral OVA challenge in EC sensitized mice is IgE-dependent

A. OVA specific IgG1 in EC sensitized IgE−/− mice and WT controls. B. Core body temperature after oral OVA challenge. C. Serum mMCP-1 level pre and 60 min post challenge. n=4–10 mice/group. Columns and bars represent mean and SEM. *** P <0.001. ns = not significant.

Figure 3
Figure 3. Response of orally immunized mice to antigen challenge

A. Experimental protocol. B. OVA-specific IgE and IgG1. C. Core body temperature after oral challenge. D. Serum mMCP-1. E, F. Core body temperature after i.v. challenge. n/group= 10–12 in A-D and 4 in E, F. Columns and bars: mean and SEM. ** P<0.01, *** P <0.001. ns = not significant.

Figure 4
Figure 4. Increased IL-4 serum levels in EC sensitized mice

A. Serum levels of IL-4 determined by IVCCA. B. IL-4 mRNA levels in MLN determined by quantitative PCR. Columns and bars represent mean and SEM.* P <0.05, *** P<0.001. ns = not significant.

Figure 5
Figure 5. Expansion of submucosal MCs in the jejunum of EC sensitized mice

A. CAE staining of jejunum from EC sensitized and orally immunized mice. Magnification 200X, Inset 400X. B–D. Total (B), mucosal (C), and submucosal (D) MCs in jejunum of EC sensitized, orally immunized, and unmanipulated mice. n= 5–10 mice/group. Columns and bars: mean and SEM. Statistical significance was calculated relative to unmanipulated group. * P <0.05, ** P <0.01.

Figure 6
Figure 6. Expansion of intestinal MCs in EC sensitized mice is IgE-dependent

Quantitation of MCs in CAE stained jejunal tissue sections from EC sensitized IgE−/− mice and unmanipulated IgE−/− controls, n= 5 mice/group. Columns and bars represent mean and SEM.

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References

    1. Hill DJ, Heine RG, Hosking CS, Brown J, Thiele L, Allen KJ, et al. IgE food sensitization in infants with eczema attending a dermatology department. J Pediatr. 2007;151:359–363. - PubMed
    1. Lack G, Fox D, Northstone K, Golding J. Factors associated with the development of peanut allergy in childhood. N Engl J Med. 2003;348:977–985. - PubMed
    1. Spergel JM, Mizoguchi E, Brewer JP, Martin TR, Bhan AK, Geha RS. Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice. J Clin Invest. 1998;101:1614–1622. - PMC - PubMed
    1. Jin H, He R, Oyoshi M, Geha RS. Animal models of atopic dermatitis. J Invest Dermatol. 2009;129:31–40. - PMC - PubMed
    1. Oettgen HC, Martin TR, Wynshaw-Boris A, Deng C, Drazen JM, Leder P. Active anaphylaxis in IgE-deficient mice. Nature. 1994;370:367–370. - PubMed

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