The Critical Role of Mast Cells in Allergy and Inflammation

Abstract

Mast cells are well known for their involvement in allergic and anaphylactic reactions, but recent findings implicate them in a variety of inflammatory diseases affecting different organs, including the heart, joints, lungs, and skin. In these cases, mast cells appear to be activated by triggers other than aggregation of their IgE receptors (FcepsilonRI), such as anaphylatoxins, immunoglobulin-free light chains, superantigens, neuropeptides, and cytokines leading to selective release of mediators without degranulation. These findings could explain inflammatory diseases, such as asthma, atopic dermatitis, coronary inflammation, and inflammatory arthritis, all of which worsen by stress. It is proposed that the pathogenesis of these diseases involve mast cell activation by local release of corticotropin-releasing hormone (CRH) or related peptides. Combination of CRH receptor antagonists and mast cell inhibitors may present novel therapeutic interventions.

Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management

“…A total of approximately 1000 bridges are necessary to induced mast cell degranulation. However, recent findings indicate that mast cells can be activated by nonallergic triggers often without degranulation, but with selective release of potent and vasoactive compounds [58]. During allergy, hypersensitivity, or anaphylaxis degranulation of mast cells takes place and a variety of stored and newly formed inflammatory mediators are released locally and in the systemic circulation.…”

Perinatal Immune Activation and Risk of Autism

“…These goals may be at least partly achieved by the use of mast cell blockers. Unfortunately, there are no clinically effective mast cell inhibitors, and the available disodium cromoglycate (cromolyn) has proven a weak inhibitor of human mast cells (Theoharides & Kalogeromitros, 2006). Instead, flavonoids such as luteolin are antiinflammatory and neuroprotective (Dirscherl et al, 2010), and can inhibit mast cell activation .…”

“…In a few studies, examination of intestinal biopsies from children with regressive autism reveals features of an autoimmune mucosal pathology, that is not seen in other conditions or inflammatory bowel diseases (Ashwood et al, 2003;Torrente et al, 2002). Many of the epidemiologic, biochemical and pathologic findings could be explained through activation of mast cells, immune cells important in both innate and acquired immunity (Galli et al, 2005), as well as in inflammation (Theoharides & Kalogeromitros, 2006). Mast cells are well-known for their leading role in allergic reactions, during which they are stimulated by IgE binding to high-affinity receptors (FcεRI), aggregation of which leads to degranulation and secretion of numerous pre-stored and newly-synthesized mediators, including IL-6 and TNF (Blank & Rivera, 2004;Kraft & Kinet, 2007;Schroeder et al, 1995;Schwartz, 1987;Serafin & Austen, 1987;Stone et al, 2010;Torigoe et al, 1997).…”

Toll-like receptors 3 ligation directly and indirectly affects mast cell cysteinyl leukotriene generation

“…Therefore, the aim of our study was to determine whether polyinosinic-polycytidylic acid (poly(I:C)), TLR3-specific synthetic analogue of viral dsRNA, can directly activate mature mast cells to degranulation as well as generation of cysteinyl LTs (cysLTs), the key mediator of inflammation [23,24]. Due to mast cells' essential role in allergic reactions [6,[8][9][10], we also examined the effect of TLR3 ligation on FcεRI-mediated mast cell response.…”

“…Moreover, mast cells also take part in different pathological processes [3,7,8], including FcεRI-mediated allergic reactions [6,[8][9][10].…”