Understanding the role of luminal antigens in IgE-mediated activation of intestinal mast cells and in allergic sensitization through the skin in Wiskott-Aldrich syndrome protein deficient mice.

Deken, M.M. (Marion) (2014) Understanding the role of luminal antigens in IgE-mediated activation of intestinal mast cells and in allergic sensitization through the skin in Wiskott-Aldrich syndrome protein deficient mice. thesis, Medicine.

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Abstract

Introduction IgE-mediated immune activation may play a role in inflammatory bowel disease. The spontaneous production of IgE antibodies against luminal food antigens in Wiskott-Aldrich syndrome protein deficient (WASP-/-) mice inquires research to provide experimental proof that IgE antibodies against luminal antigens are necessary to mediate intestinal mast cell degranulation. Besides mucosal exposure, the skin could also be an important route of sensitization to food antigens. Therefore this experiment also studies skin sensitization as a possible efficient route for the induction of food allergy and the interplay with the development of atopic dermatitis in WASP-/- mice. Materials & Methods Mast cell degranulation of the bone marrow-derived mast cells (BMMCs) of wild type and WASP-/- mice cross linked with IgE against food antigens is measured in two different assays with the release of β-hexosaminidase and detection of LAMP-1 of the surface of activated cells. Wild type en WASP-/- mice are epicutaneous sensitized with ovalbumin (OVA) through patch-treatment for three 1-weeks exposures where after mRNA expression of MCTP-1, IL-4 and IL-13 of patched and unpatched skin and serum IgE-levels are measured to determine dermatitis. Results There was no significant difference between the β-hexosaminidase release of the BMMCs with cross linking of IgE with antigen and the cells without cross linking, there is also no significant difference in release between BMMCs of wild type and WASP-/- mice or between the different concentrations of antigen. In the LAMP-1 degranulation assay there was a 13.5% detection of anti-LAMP-1 in the BMMCs of wild type mice in comparison to 5.5% detection in BMMCs of WASP-/- mice. OVA-epicutaneous sensitized wild type and WASP-/- mice had elevated serum levels of total IgE, OVA-specific IgE and IgG1, with no significant difference between the wild type and WASP-/- mice. There was no significant difference in mRNA expression of MCTP-1, IL-4 or IL-13 between skin of the unpatched and patched area, with also no difference within the wild type or WASP-/- mice. Conclusion We presume that IgE antibodies against luminal antigens mediate intestinal mast cell degranulation, especially in WASP-/- mice. Although the mice were epicutaneous sensitized to OVA, there were no signs of dermatitis in the skin of the mice. Further research in both studies is desirable.

Item Type:	Thesis (Thesis)
Supervisor name:	IJzendoorn, S.C.D. van
Supervisor name:	Fiebiger, E. PhD and Fiebiger Laboratory and Boston Children’s Hospital, Boston and States of America
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:43
Last Modified:	25 Jun 2020 10:43
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/447

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