Mast cells as cellular sensors in inflammation and immunity

Abstract

Mast cells are localized in tissues. Intense research on these cells over the years has demonstrated their role as effector cells in the maintenance of tissue integrity following injury produced by infectious agents, toxins, metabolic states, etc. After stimulation they release a sophisticated array of inflammatory mediators, cytokines, and growth factors to orchestrate an inflammatory response. These mediators can directly initiate tissue responses on resident cells, but they have also been shown to regulate other infiltrating immune cell functions. Research in recent years has revealed that the outcome of mast cell actions is not always detrimental for the host but can also limit disease development. In addition, mast cell functions highly depend on the physiological context in the organism. Depending on the genetic background, strength of the injurious event, the particular microenvironment, mast cells direct responses ranging from pro- to anti-inflammatory. It appears that they have evolved as cellular sensors to discern their environment in order to initiate an appropriate physiological response either aimed to favor inflammation for repair or at the contrary limit the inflammatory process to prevent further damage. Like every sophisticated machinery, its dysregulation leads to pathology. Given the broad distribution of mast cells in tissues this also explains their implication in many inflammatory diseases.

Formononetin ameliorates mast cell‑mediated allergic inflammation via inhibition of histamine release and production of pro‑inflammatory cytokines

“…Mast cells are the effector cells during the mediation of allergic inflammation. Following exposure to external allergens, the cross-linking of immunoglobulin (Ig) E antibodies occurs and leads to aggregations of the IgE specific receptor (FcεR), which binds to the surface of mast cells (1). Subsequently, histamine is released and cytokines, chemokines, proteases and eicosanoids are secreted following the degranulation of mast cells (2).…”

Inflammation and Chronic Pelvic Pain: A Biological Trigger for Depression in Women?

“…MCs behave as cellular sensors, directing tissue responses in peripheral inflammation [13,14]. Their activity can be initiated after tissue injury [13], in response to certain metabolic conditions [29], through hormonal signals [30], or by signals originating from the nervous system [31].…”

“…In the brain, MCs reside on the brain side of the blood-brain barrier and interact with neurons, glia, blood vessels, and other hematopoietic cells via their neuroactive prestored and newly synthesized mediators [13,14]. They are first responders, acting as catalysts and recruiters to initiate, amplify, and prolong other immune and nervous responses upon activation [16].…”

“…Their activity can be initiated after tissue injury [13], in response to certain metabolic conditions [29], through hormonal signals [30], or by signals originating from the nervous system [31]. When activated, MCs rapidly release preformed mediators that include histamine, heparin, serotonin, chemotactic factors and various proteases such as peroxidase, tryptase, chymase, carboxidase, and beta-glucuronidase, and tumor necrosis factor alpha (TNF-α) [32].…”

“…Immune system dysregulation is emerging as a common event in these conditions. In particular, Mast Cells (MCs) are now considered as cellular sensors in inflammation and immunity [13], as coordinators of peripheral inflammatory processes [14], and as important players in the development and maintenance of neuroinflammation due to their capacity to directly or indirectly interact with glial cells [15][16][17]. MCs might pilot the persistent lowgrade inflammation which is present both in chronic pain and mood disorders such as anxiety and depression.…”