Calcium and mast cell activation

I. Frydas

Faculty of Parasitology, Aristotle University of Thessaloniki, Macedonia, Greece



            Bone mineral density is decreased in inflammatory states, and the causes of this decrease have multiple aspects including insufficiency of nutritional intake, maalbsorption and dysfunction of the immune system. In inflammatory states, calcium malabsorption causes slightly increased fracture risk, demonstrating that the pathophysiology of bone loss is correlated to clinical aspects. Therefore, Ca malabsorption is related the incapacity to achieve the potential bone mass peak. Ca(2+) is an important intracellular second messenger in many cell types, and regulates many cellular processes, such as cell activation and proliferation. In inflammatory diseases, such as asthma, calcium regulation is altered along with other parameters. These promote hyperactivity and remodeling of the airway walls. Inflammation is related to RANKL secretion, osteoclast activation and augumentation of bone resorption. Calcium production stimulates the generation of cyclic ADP and increased TNF with the participation of MAPK, NF-kB and AP-1. The inflammasome is a proteolytic complex that regulates IL-1β generation  in mast cells and other immune cells. Mast cell activation is a central process in the initiation of inflammatory diseases, and plays a central role in adaptive and innate immunity. In addition, immunoglobulin E (IgE) and mast cells (MCs) are important participants in allergic diseases. IgE bind FcεRI and activate a complex regulatory network that leads to MC activation and the inflammatory process. MC activation depends on an increase in the intracellular Ca(2+) concentration, and influx of Ca(2+) from the extracellular space to intracellular entrance which is required for the full activation, although released Ca(2+) activates Ca(2+) channels which are implicated in the excitability of the cells. The Ca²⁺ activation  in the endoplasmic reticulum is regulated by mitochondria. Mitochondria take up Ca2+ released from the endoplasmic reticulum by IP₃ receptors, leading to channel activations. These processes lead to MC enzyme activation, secretion and gene expression. Therefore, mitocondrial regulation channels contribute to the  intracellular Ca²⁺ signalling. These findings indicated that calcium is involved in regulating NF-κB signaling. Here, we describe our current understanding of Ca2+ signaling, and its role in mast cell signaling and survival.

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