Allergen-induced bronchial hyperreactivity and eosinophilic inflammation occur in the absence of IgE in a mouse model of asthma

Abstract

In patients with asthma, elevations of IgE correlate both with allergic inf lammation of the airways and with bronchial hyperreactivity (BHR). Several investigations, using mouse models of this disease, have indicated a central role for IgE in the pathogenesis of the eosinophilic inf lammation as well as in the obstructive airway physiology of BHR. Some diagnostic studies and therapeutic strategies for asthma are based on the putative role of IgE in asthma pathogenesis. Here, we use mice with a null mutation of the C locus to show that bronchial inf lammation and BHR in response to allergen inhalation both can occur in the absence of IgE. We demonstrate that the eosinophilic bronchial inf lammation elicited in an established mouse model of hypersensitivity to Aspergillus fumigatus (Af) is accompanied by the asthmatic physiology of BHR. Wild-type and IgE-deficient mice were sensitized intranasally with Af extract. Both groups of animals developed bronchoalveolar lavage eosinophilia and pulmonary parenchymal eosinophilia. This was accompanied by increased serum levels of total and Af-specific IgE in the wild-type animals only. This Af-sensitization protocol resulted in significant BHR in both wild-type mice and IgE-deficient mice. Interestingly, unsensitized IgE-deficient mice had increased bronchial responsiveness compared with unsensitized wildtype controls. We conclude that BHR and airways inf lammation can be fully expressed via IgE-independent mechanisms. These may involve the activation of mast cells by factors other than IgE as well as a mucosal lymphocyte-mediated immune response to allergen.

CC Chemokine Receptor-2 Is Not Essential for the Development of Antigen-Induced Pulmonary Eosinophilia and Airway Hyperresponsiveness

“…Mast cells and IgE are believed to play an important role in models where sensitization and challenge are relatively attenuated (40 -42). In contrast, in protocols that use repeated airway challenges in sensitized mice, AHR and pulmonary eosinophilia develop independently of IgE, B cells, and mast cells, suggesting a primary role for T cells in these models (32,(42)(43)(44)(45). This may explain the differences seen between our studies (multiple challenge model) and those of Campbell et al (single-challenge model) (38).…”

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

“…However, OVA is capable of inducing all of these allergic changes if given remote from the lung in a series of priming doses, typically with aluminum-based adjuvants before intrapulmonary challenge (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). In contrast, the other major class of allergen, in this study termed type II, is derived from the fungus Aspergillus fumigatus and readily induces allergic lung inflammation when given only through the airway and without the need for additional adjuvant (12)(13)(14). Although A. fumigatus-based allergens are derived from an organism strongly linked to human allergic illness (15) and induce lung disease with a physiologically more relevant protocol, experimentally OVA is used far more often.…”

Intratracheal Priming with Ovalbumin- and Ovalbumin 323–339 Peptide-Pulsed Dendritic Cells Induces Airway Hyperresponsiveness, Lung Eosinophilia, Goblet Cell Hyperplasia, and Inflammation

“…In contrast to human asthma, asthma-like diseases in the mouse do not require the participation of IgE (2,3,(31)(32)(33). The presence of B cells is also not a prerequisite for the induction of asthmarelated symptoms (34).…”