The mast cell and allergic diseases: role in pathogenesis and implications for therapy

Abstract

SummaryMast cells have long been recognized for their role in the genesis of allergic inflammation; and more recently for their participation in innate and acquired immune responses. Mast cells reside within tissues including the skin and mucosal membranes, which interface with the external environment; as well as being found within vascularized tissues next to nerves, blood vessels and glandular structures. Mast cells have the capability of reacting both within minutes and over hours to specific stimuli, with local and systemic effects. Mast cells express the high affinity IgE receptor (FceRI) and upon aggregation of FceRI by allergen-specific IgE, mast cells release and generate biologically active preformed and newly synthesized mediators which are involved in many aspects of allergic inflammation. While mast cells have been well documented to be essential for acute allergic reactions, more recently the importance of mast cells in reacting through pattern recognition receptors in innate immune responses has become recognized. Moreover, as our molecular understanding of the mast cell has evolved, novel targets for modulation have been identified with promising therapeutic potential.

Cigarette smoke exacerbates mouse allergic asthma through Smad proteins expressed in mast cells

“…Mast cells have been implicated in airway inflammation and remodeling [24,26], but long-term smoking (4 mo) did not show enhanced numbers of mast cells in OVA-induced lung tissues in vivo [13]. In contrast to these findings, we observed that smoke elevated the numbers of mast cells in BAL cells and lung tissues of OVA/S mice, although both studies differed in various factors such as smoke exposed periods and allergen challenge.…”

“…Mast cells are activated by cross-linking of antigen-specific IgE bound to the high-affinity receptor (FcεRI) on their membranes. Activated mast cells secrete preformed mediators (histamine, tryptase, chymase, TNFα, and other proteins) as well as newly synthesized proinflammatory mediators such as PGD2, leukotrienes, cytokines, and chemokines [24]. These mediators contribute to airway inflammation and remodeling in allergic asthma [24,25].…”

“…Activated mast cells secrete preformed mediators (histamine, tryptase, chymase, TNFα, and other proteins) as well as newly synthesized proinflammatory mediators such as PGD2, leukotrienes, cytokines, and chemokines [24]. These mediators contribute to airway inflammation and remodeling in allergic asthma [24,25]. TGF-β also acts as a negative regulator of mast cell function, TGF-β/Smad3-mediated signaling is essential for maximal cell growth in mast cells [26] and mast cell development via p38 kinase [27].…”

Effects of intra-amniotic lipopolysaccharide exposure on the fetal lamb lung as gestation advances

“…Mast cells in the lower airways contribute to the development of asthma and allergic diseases (26). Mast cells are of interest because of a possible relation between chorioamnionitis, preterm birth, and the development of asthma later in life (27,28).…”

Transcriptome sequencing (RNA-Seq) of human endobronchial biopsies: asthmaversuscontrols

“…It has been shown that increased expression of the T-helper cell (Th)2-cytokines interleukin (IL)-4 and IL-13 not only promotes eosinophilic inflammation, but also activates mast cells [6], and that microlocalisation of these mast cells predominantly in the ASM layer is a key factor in the pathophysiology of asthma [7]. Activated mast cells release various mediators, which can lead to enhanced ASM contraction and proliferation [6,8]. Interestingly, gene expression analysis has shown that the degree of Th2-cytokine expression in bronchial biopsies varies between asthma patients, being associated with aspects of airway remodelling and responsiveness to inhaled steroids [9].…”