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IgE Influences the Number and Function of Mature Mast Cells, but Not Progenitor Recruitment in Allergic Pulmonary Inflammation¹

Clinton B. Mathias^*,, Eva-Jasmin Freyschmidt^*,, Benjamin Caplan^*, Tatiana Jones, Dimitri Poddighe^*,, Wei Xing, Krista L. Harrison^*, Michael F. Gurish^, and Hans C. Oettgen^2,*,

^* Division of Immunology, Children’s Hospital, Boston, MA 02115; Division of Rheumatology, Allergy, and Immunology, Brigham and Women’s Hospital, Boston, MA 02115; and Harvard Medical School, Boston, MA 02115

Studies performed using cultured cells indicate that IgE functions not only to trigger degranulation of mast cells following allergen exposure, but also to enhance their survival. Such an influence of IgE on mast cell homeostasis during allergic responses in vivo has not been established. In this study, we show that inhalation of Aspergillus fumigatus extract in mice induced a dramatic rise in IgE accompanied by an increase in airway mast cells. These had an activated phenotype with high levels of FcRI. Plasma mast cell protease-1 was also increased, indicating an elevated systemic mast cell load. In addition, enhanced levels of IL-5 and eosinophils were observed in the airway. Both mast cell expansion and activation were markedly attenuated in IgE^–/– animals that are incapable of producing IgE in response to A. fumigatus. The recruitment of eosinophils to the airways was also reduced in IgE^–/– mice. Analyses of potential cellular targets of IgE revealed that IgE Abs are not required for the induction of mast cell progenitors in response to allergen, but rather act by sustaining the survival of mature mast cells. Our results identify an important role for IgE Abs in promoting mast cell expansion during allergic responses in vivo.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the following National Institutes of Health grants: National Institute of Allergy and Infectious Diseases Grants R01-AI054471 (to H.C.O.) and P01 AI 031599 (to M.F.G.). This work was also supported by a research grant from Novartis Pharmaceuticals.

² Address correspondence and reprint requests to Dr. Hans C. Oettgen, Division of Immunology, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115. E-mail address: hans.oettgen{at}childrens.harvard.edu

³ Abbreviations used in this paper: MNC, mononuclear cell; Af, Aspergillus fumigatus; BAL, bronchoalveolar lavage; BHR, bronchial hyperresponsiveness; BMMC, bone marrow-derived mast cell; Lin, Lineage; MCp, mast cell progenitor; NS, normal saline; SCF, stem cell factor; SM, staining medium; WT, wild type.