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Increased airway responsiveness, allergy-type-I skin responses and systemic anaphylaxis in a humanized-severe combined immuno-deficiency mouse model

Authors


Udo Herz, Department of Clinical Chemistry and Molecular Diagnostics, Hospital of the Philipps-University Marburg, Baldingerstraße, 35033 Marburg, Germany. E-mail: herzu@med.uni-marburg.de

Summary

Background In patients with allergic bronchial asthma, a strong relationship between elevated serum IgE antibody titres and the development of increased airway responsiveness (AR) has been demonstrated. To further elucidate the relationship between human (hu) IgE and development of increased AR, we developed an in vivo model utilizing immuno-compromised severe combined immuno-deficiency (SCID) mice.

Methods SCID mice were either reconstituted with peripheral blood mononuclear cells (PBMC) from non-atopic, healthy or atopic individuals sensitized against house dust mite allergen (Der p), or passively sensitized with plasma from non-atopic, healthy or atopic individuals.

Results In both systems, atopic hu-SCID mice developed increased AR. The following results suggest that these responses were mediated via IgE antibodies: increased AR did not occur after transfer of either PBMC or IgE-negative plasma from non-atopic individuals; increased AR occurred simultaneous with increased serotonin release detected 15 min after allergen–aerosol challenge in bronchoalveolar lavage fluid; and increased AR required at least two allergen–aerosol challenges. SCID mice reconstituted with serum containing anti-Der p IgE antibodies developed positive immediate-type skin test responses to intradermal injection of Der p as well as anti-hu-IgE antibody. In addition, IgE binding to skin mast cells was demonstrated by immunohistochemistry. Furthermore, intravenous challenge of hu anti-Der p positive SCID mice with Der p resulted in systemic anaphylaxis.

Conclusion These data provide evidence that passive immunization of SCID mice with hu IgE alters AR and that T cells and eosinophils were not a requirement for the development of increased AR in this model.

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