Mast cell plasticity and sphingosine-1-phosphate in immunity, inflammation and cancer

Mast cells (MC) are found in all vascularized tissues at homeostasis and, until recently, were viewed only as effector cells of allergic reactions via degranulation, the canonical process through which MC release mediators, including histamine and pre-formed proteases and cytokines such as TNF. Cross-linking of IgE bound to surface high affinity receptors for IgE (FcɛRI) by a specific antigen (Ag) triggers signaling events leading to degranulation. We and others have reported the concomitant production and export of an influential multifaceted sphingolipid mediator, sphingosine-1-phosphate (S1P) transported outside of MC by ATP-binding cassettes (ABC) transporters, i.e., independently of degranulation. Indeed, the MC horizon expanded by the discovery of their unique ability to selectively release mediators depending upon the stimulus and receptors involved. Aside from degranulation and transporter usage, MC are also endowed with piecemeal degranulation, a slower process during which mediator release occurs with minor morphological changes. The broad spectrum of pro- and anti-inflammatory bioactive substances MC produce and release, their amounts and delivery pace render these cells bona fide fine-tuners of the immune response. In this viewpoint article, MC developmental, phenotypic and functional plasticity, its modulation by microRNAs and its relevance to immunity, inflammation and cancer will be discussed.