An Essential Role of Mast Cells in the Development of Airway Hyperresponsiveness in a Murine Asthma Model

Abstract

Immunization of BALB/c mice with alum-adsorbed OVA, followed by three bronchoprovocations with aerosolized OVA, resulted in the development of airway hyperresponsiveness (AHR) and allergic inflammation in the lung accompanied by severe infiltration of eosinophils into airways. In this murine asthma model, administration of monoclonal anti-IL-5 Ab before each Ag challenge markedly inhibited airway eosinophilia, but the treatment did not affect the development of AHR. Immunization and aerosol challenges with OVA following the same protocol failed to induce AHR in the mast cell-deficient W/Wv mice, but induced AHR in their congenic littermates, i.e., WBB6F1 (+/+) mice. No significant difference was found between the W/Wv mice and +/+ mice with respect to the IgE and IgG1 anti-OVA Ab responses and to the airway eosinophilia after Ag provocations. It was also found that reconstitution of W/Wv mice with bone marrow-derived mast cells cultured from normal littermates restored the capacity of developing Ag-induced AHR, indicating that lack of mast cells was responsible for the failure of W/Wv mice to develop Ag-induced AHR under the experimental conditions. However, the OVA-immunized W/Wv mice developed AHR by increasing the frequency and Ag dose of bronchoprovocations. The results suggested that AHR could be developed by two distinct cellular mechanisms. One would go through mast cell activation and the other is IgE/mast cell independent but an eosinophil/IL-5-dependent mechanism.

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

“…Recently, strong evidence has been presented that ties the role of mast cells in murine models of asthma to the experimental protocols used. Thus, Kobayashi et al (17) noted that mast cell-deficient mice developed reduced AHR compared with normal congenic mice only under certain experimental conditions. They proposed that AHR could be induced by different mechanisms, and only certain protocols would enlist mechanisms that involve IgE-mediated mast cell activation.…”

“…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

“…Some reports have demonstrated that mast cell activation results in a potentiation of late AHR [8][9][10], and mast cells have been reported to represent a potential source of TNF-a in vitro [11,12]. These findings suggest that TNF-a plays a role in mast cellmediated late AHR.…”

“…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.…”

Potential Role of Serum Periostin in the Early Detection of Bronchial Asthma in Children

“…При аллергической БА пролиферация Th2 лимфоцитов и синтез интерлейки-на (Interleukin, IL) 4 активированными тучными клетка-ми способствует переключению изотипа В лимфоцитов на синтез иммуноглобулина (Immunoglobulin, Ig) E. С пози-ций современных данных, активация тучных клеток анти-телами IgE не ограничивается реакцией немедленного типа при встрече с установленным аллергеном. Тучные клетки играют важную роль в развитии хронического воспаления дыхательных путей, опосредованного синте-зом IL4, IL5 и IL13, которые в свою очередь стимулируют пролиферацию Th2 лимфоцитов, дальнейший синтез IgE-антител, рекрутирование и дифференцировку эозинофи-лов [10]. Установлено, что инфильтрация респираторного тракта дыхательных путей эозинофилами и последующая их дегрануляция сопровождаются высвобождением цито-токсических продуктов (эозинофильные катионные бел-ки, нейротоксины, пероксидазы), которые вносят зна-чительный вклад в повреждение эпителия дыхательных путей, гиперпродукцию слизи бокаловидными клетками, бронхиальную гиперреактивность и нарушение функ-ции мерцательного эпителия.…”