Dissociation of Airway Hyperresponsiveness from Immunoglobulin E and Airway Eosinophilia in a Murine Model of Allergic Asthma

Abstract

Nonspecific airway hyperresponsiveness (AHR) is a hallmark of human asthma. Both airway eosinophilia and high serum levels of total and antigen-specific immunoglobulin E (IgE) are associated with AHR. It is unclear, however, whether either eosinophilia or increased IgE levels contribute directly to, or predict, the development of AHR. Investigations conducted with various murine models of asthma and different mouse strains have resulted in conflicting evidence about the roles that IgE and airway eosinophilia play in the manifestation of AHR. We show that systemic priming with ovalbumin (OVA) in alum, followed by a single day of OVA aerosol challenge, is sufficient to induce AHR, as measured by increased pulmonary resistance in response to intravenously delivered methacholine in BALB/c, but not C57BL/6 or B6D2F1, mice. This was observed despite the fact that OVA-challenged BALB/c mice had less airway eosinophilia and smaller increases in total IgE than either C57BL/6 or B6D2F1 mice, and had less pulmonary inflammation and OVA-specific IgE than B6D2F1 mice. We conclude that airway eosinophilia, pulmonary inflammation, and high serum levels of total or OVA-specific IgE are all insufficient to induce AHR in C57BL/6 and B6D2F1 mice, whereas BALB/c mice demonstrate AHR in the absence of airway eosinophilia. These data confirm that the development of AHR is genetically determined, not only in naive mice, but also in actively immunized ones, and cannot be predicted by levels of airway eosinophilia, pulmonary inflammation, total IgE, or antigen-specific IgE.

Airway Hyperresponsiveness, Late Allergic Response, and Eosinophilia Are Reversed with Mycobacterial Antigens in Ovalbumin-Presensitized Mice

“…This is consistent with the reports of other investigators who have shown that IgE is not required for the development of eosinophilic airway inflammation and AHR in mice (21,(25)(26)(27). This could also be true in humans as observed by Haselden et al (28).…”

“…Indeed, many reports have also positively correlated eosinophils and/or IL-5 with AHR (18 -20). However, there have been negative reports as well, suggesting that eosinophils are neither required nor sufficient to induce AHR (21). In other reports, treatment with mAb to IL-5 had no effect on the reversal of established AHR in mice (22) and humans (23) despite complete suppression of eosinophil accumulation of airway tissue.…”

Acellular Pertussis Vaccine Protects against Exacerbation of Allergic Asthma Due toBordetella pertussisin a Murine Model

“…Th2 responses are thought to be protective against parasite-mediated disease (60) but are associated with allergic disorders (59,61). It has been suggested that induction of Th2 cells or failure to mount a Th1 or regulatory T-cell response to foreign antigens in childhood may enhance atopic disease (10,49).…”

“…Asthma is a chronic disease of the respiratory tract and is tightly associated with airway hyperresponsiveness, increased mucus production, and infiltration of the bronchial mucosa by CD4 ϩ T cells (59). In allergic asthma there is evidence of an altered local T-cell response in favor of Th2 cytokines (interleukin-4 [IL-4], IL-5, and IL-13), which results in B-cell isotype switching to immunoglobulin E (IgE); mast cell, eosinophil, and basophil recruitment; and the production of a wide range of inflammatory mediators (61).…”

Adenovirus expressing Fas ligand gene decreases airway hyper-responsiveness and eosinophilia in a murine model of asthma

“…11,12 However, the transfer of eosinophils to IL-5 À/À mice overcomes the intrinsic defect in T cell IL-13 production 13 and induces the development of AHR. 8 Thus, although the role of IL-5 in AHR is controversial, [6][7][8][9][14][15][16] the relationship between eosinophils and AHR is still correlative. 8,[11][12][13] Apoptosis is an important mechanism for the maintenance of homoeostasis in the immune system.…”