Development of Eosinophilic Airway Inflammation and Airway Hyperresponsiveness in Mast Cell–deficient Mice

Abstract

Mast cells are the main effector cells of immediate hypersensitivity and anaphylaxis. Their role in the development of allergen-induced airway hyperresponsiveness (AHR) is controversial and based on indirect evidence. To address these issues, mast cell–deficient mice (W/W v) and their congenic littermates were sensitized to ovalbumin (OVA) by intraperitoneal injection and subsequently challenged with OVA via the airways. Comparison of OVA-specific immunoglobulin E (IgE) levels in the serum and numbers of eosinophils in bronchoalveolar lavage fluid or lung digests showed no differences between the two groups of mice. Further, measurements of airway resistance and dynamic compliance at baseline and after inhalation of methacholine were similar. These data indicate that mast cells or IgE–mast cell activation is not required for the development of eosinophilic inflammation and AHR in mice sensitized to allergen via the intraperitoneal route and challenged via the airways.

IgE-Dependent Mast Cell Activation Potentiates Airway Responses in Murine Asthma Models

“…Indeed, there are studies supporting the role of mast cells in these models (10,11). However, there are other reports in the literature that question mast cell participation in this response (12)(13)(14)(15). Recently, strong evidence has been presented that ties the role of mast cells in murine models of asthma to the experimental protocols used.…”

“…While some reports have demonstrated that mast cell deficiency results in attenuated eosinophilic airway inflammation (10,11), others have shown that this deficiency does not affect allergic airway inflammation and AHR (12)(13)(14)(15). Recent studies have suggested that the extent to which mast cells contribute to airway inflammation and AHR in mice is highly dependent on the experimental model used to generate the airway response (16,17).…”

Mast cells play a key role in the developmentof late airway hyperresponsiveness through TNF‐αin a murine model of asthma

“…While some reports have demonstrated that mast cell activation results in a potentiation of late AHR [8][9][10], others have shown that AHR can be elicited in the absence of IgE Ab [17,18] or mast cells [19], dependent on the experimental model used to generate the airway response. These data have come from studies that used a protocol that consists of airway antigen challenge for more than 3 consecutive days, and examination of AHR usually 2 days after the last antigen challenge.…”

“…AHR was also assessed as a change in airway function after challenge with aerosolized methacholine via airways, as described elsewhere [39,40]. Anesthesia was achieved with 80 mg/kg of pentobarbital sodium injected i.p.…”

From IgE to Anti‐IgE: Where do we stand?

“…There are quite a lot of evidential data demonstrating a pivotal role for IgE in the development of bronchial asthma: increased IgE serum levels are associated with prevalence rates and disease severity (31,32), asthma in children is almost always associated with production of allergen-specific IgE and positive skin test reactivity against environmental allergens (8,31), and even in patients with non-allergic asthma, despite normal IgE serum levels, an extensive production of IgE in large areas of the airways has been found (36). On the other hand, experimental data from murine models demonstrate that development of airway inflammation and hyperreactivity to unspecific stimuli, two of the three main features of the disease, may occur independently of B cells (78), IgE-production (78,79) or IgE-mediated mast-cell activation (80). Concordantly, in animals with a robust allergen-mediated inflammatory response of the airways, treatment with anti-IgE antibodies does not inhibit development of airway inflammation or hyperreactivity (81).…”