Novel Strategies to Target Mast Cells in Disease

Abstract

Mast cells (MCs) are versatile effector cells of the immune system, characterized by a large content of secretory granules containing a variety of inflammatory mediators. They are implicated in the host protection toward various external insults, but are mostly well known for their detrimental impact on a variety of pathological conditions, including allergic disorders such as asthma and a range of additional disease settings. Based on this, there is currently a large demand for therapeutic regimens that can dampen the detrimental impact of MCs in these respective pathological conditions. This can be accomplished by several strategies, including targeting of individual mediators released by MCs, blockade of receptors for MC-released compounds, inhibition of MC activation, limiting mast cell growth or by inducing mast cell apoptosis. Here, we review the currently available and emerging regimens to interfere with harmful mast cell activities in asthma and other pathological settings and discuss the advantages and limitations of such strategies.

Mast Cell Proteases Tryptase and Chymase Induce Migratory and Morphological Alterations in Bronchial Epithelial Cells

“…In the healthy human lung, the MC T is the dominating subtype and is readily found in structures such as bronchial mucosa and alveolar parenchyma [ 7 , 8 ]. In various pathological conditions of the lung, such as severe asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF) and idiopathic pulmonary fibrosis (IPF) the number of MC TC increase and also home into structures that normally have very few MCs, such as the bronchial epithelium [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. The role of intraepithelial MCs and the phenotypic change from MC T to MC TC in airway pathology is, to this point, unknown.…”

Tuo-Min-Ding-Chuan Decoction Alleviate Ovalbumin-Induced Allergic Asthma by Inhibiting Mast Cell Degranulation and Down-Regulating the Differential Expression Proteins

“…MC exists in almost all vascularized tissues and is a potential source of many bioactive secretory products, including cytokines and growth factors ( Mukai et al, 2018 ). The differential expression proteins found in animal experiments are directly or indirectly related to the activation and recruitment of MC, for example, MCP-1, CCL5 and OPN can be released from MC ( Zhang et al, 2011 ; Mukai et al, 2018 ; Paivandy and Pejler, 2021 ). Therefore, we speculated that TMDCD may inhibit MC degranulation.…”

“…MC exists in almost all vascularized tissues and is a potential source of many bioactive secretory products, including cytokines and growth factors (Mukai et al, 2018). The differential expression (Zhang et al, 2011;Mukai et al, 2018;Paivandy and Pejler, 2021). Therefore, we speculated that TMDCD may inhibit MC degranulation.…”

The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

“…Ketotifen, an H1 antihistamine and MC stabilizer, is known to relieve some of the allergic symptoms in AD. However, other MC stabilizers have limited efficacy in AD, such as sodium cromoglycate and nedocromil sodium [189,190]. New agents targeting the reduction of MCs have potential roles in the treatment of AD [191].…”