Targeting Mast Cells in Human Disease: Bridging Pathology and Therapy

Dear Colleague,

Mast cells (MCs) are normally present in different tissues and are involved in several allergic, non-allergic, and inflammatory processes. In recent years, the effects of the altered activation of MCs have become better understood: their activation releases inflammatory mediators, such as histamine, prostaglandins, serotonin and tryptase, leading to alterations in barrier function, vascular mucosal permeability, hormone secretion, and pain perception threshold.

MC ubiquity is responsible for the pleomorphic clinical symptoms of MC activation, which can involve virtually all organ systems. Anaphylaxis is the most recognizable manifestation of MC activation; recurrent severe clinical manifestations of anaphylaxis are referred to as mast cell activation syndrome (MCAS). Other clinical symptoms may largely overlap among several disorders despite having different underlying pathogenetic mechanisms.

Various combinations of local and systemic activation are linked to different degrees of tissue-specific consequences. MC hyperactivity is thought to play a role in irritable bowel syndrome, as MCs are reported to be a prevalent component of the inflammatory infiltrate. MCs are also involved in physiological female reproductive functions, as modifications to their morphology, granule content, and activation have been reported across all stages of the menstrual cycle and during pregnancy and may play a role in local disfunction. Recently, several reports have highlighted MC mediator release in the pathogenesis of the coronary artery vasospasm known as Kounis syndrome.

Finally, the proliferation and infiltration of tissue by clonal MCs are referred to as mastocytosis, a condition that can be further defined according to organ involvement with or without organ disfunction.

Therapeutic approaches to MC disorders are diverse and based on the pathogenetic mechanisms driving them. Nonetheless, improving our knowledge on the role of MC activation across different pathogenetic pathways may lead to advances in the treatment of several diseases.

Dr. Marianna Criscuolo
Guest Editor

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• mast cell
• mast cell activation syndrome
• anaphylaxis
• mastocytosis
• anti-mediator therapy