Evidence suggests that well-known mast cell mediators, such as histamine and bioactive lipids, are responsible for many of the physiological effects observed in the acute phase of allergic reactions. Mast cells located in different compartments in the lung and airways have different characteristics and express different mediators.
Therefore, the accumulation of mast cells at sites of the allergic lung is likely relevant to the asthma phenotype, severity, and progression, researchers hypothesized.
For a review published in Frontiers in Immunology, they summarized research with implications on the role and development of mast cells and their progenitors in allergic asthma and covered selected activation pathways and mast cell mediators that have been implicated in the pathogenesis. They focused on describing mechanisms identified using in vivo mouse models and data obtained by analysis of clinical samples.
A high frequency of circulating human mast cell progenitors may reflect ongoing pathological changes in the allergic lung, the researchers explained. In allergic asthma, mast cells become activated mainly via IgE-mediated crosslinking of the high affinity receptor for IgE (FcεRI) with allergens. However, mast cells can also be activated by numerous other stimuli, including toll-like receptors and MAS-related G protein-coupled receptor X2.
Patients With Asthma May Differ in Degree of Mast Cell Involvement
“Asthma is a heterogenous disease highlighted by the differences in time of onset, severity, inflammatory pattern, and responsiveness to corticosteroid treatment,” the study authors noted. “Similarly, patients with asthma may differ in whether or not mast cells play a major or minor role in the pathogenesis. Given the plentitude of mediators that mast cells secrete, the limited beneficial effect of histamine receptor antagonists it is not surprising. It will likely be impossible to efficiently treat allergic asthmatics by targeting another single mast cell mediator. Still, the success of omalizumab as a treatment for a subgroup of patients with allergic asthma with severe or persistent symptoms indicates an IgE-mediated mast cell-involvement in their disease”
The next step, they added, will be determining what other triggers of mast cell activation that may cause symptoms in different sub-groups of allergic asthmatics would be a better strategy for the development of novel drugs targeting mast cells. “Recent advances suggest that resident connective tissue-type mast cells are mainly self-sustained and of fetal origin,” they wrote. “In the lung of patients with allergic asthma, mast cells accumulate in the smooth muscles, bronchial epithelium, and alveolar parenchyma. The unique location of these lung mast cells can be replicated using mouse models of allergic asthma, and in these models, the accumulation of mast cells is preceded by the recruitment of mast cell progenitors to the lung. Although studies using mast cell-deficient mice subjected to allergic airway inflammation protocols have defined many new possible mechanisms that may occur in the human disease, these mechanisms need to be re-evaluated using the new Kit-independent mast cell-deficient strains to try and clarify the role of mast cells in allergic airway inflammation.”
