The Effect And Mechanism Of Extracellular Ca²⁺on The Food Allergic Reaction

On the basis of numerous studies of the current epidemiology of food allergy over the past 3 years,food allergy has seriously affects nearly 5%of adults and 8%of children's normal life,with growing evidence of an increase in prevalence.In the food allergy mechanism,Ca2+,as an intersection in many classic cellular signal pathways,can convert the extracellular signal received from cell surface receptor into the intracellular signal,which is the key to the happen of food allergic reaction.On the one hand,the release of mediators and granule-plasma membrane fusion are completely dependent on intracellular Ca2+ by both microtubule formation and F-actin ring disassembly in Fc?RI-mediated degranulation;on the other hand,both the production and secretion of cytokines and eicosanoids are in a calcium-manner by activating nuclear factor of activated T-cells and mitogen-activated protein kinase signalings.Under normal conditions,the concentration of extracellular Ca2+ is regulated by homeostasis,which usually varies between 0.9 mM and 1.2 mM.However,necrotic cells can release intracellular Ca2+ to the body fluid after the body becomes infected,causing the rapid increase of Ca2+ concentration at the point of infection.And the increased extracellular Ca2+ can active other cells around the inflection site including mastcells and basophils which both are the main effector cells in allergic reaction.Therefore infers from this:as the body becomes infected,necrotic cells will release its intracellular Ca2+ to the body fluid causing the rapid increase of extracellular Ca2+ at the inflection site,which will active the mast cells and basophils around the inflection to aggravate the occurrence and development of food allergy.In this research,rat basophilic leukemia-2H3(RBL-2H3),mouse bone marrow-derived mast cells(BMMCs)and passive systemic allergic reaction in Balb/c mice were used to study the effect of the increased extracellular Ca24+ on the occurrence and development of allergic reaction,and the key target of extracellular Ca2+ on the effector cells and its downstream signaling pathways.Otherwise,the mechanisms of non-depleting CD4-blockade and glycyrrhizic acid in the glycyrrhiza on the food allergic reaction were also elucidated from the perspective of Ca2+ mobilization.The purpose of this research is to illuminate the immunological mechanism of the occurrence and development of food allergy and the key role of Ca2+ in the immune response.The main results and conclusions are as follows:(1)Determine the necrotic cells can release intracellular Ca2+ to the body fluid causing the rapid increase of extracellular Ca2+ concentration around the inflection site,which have an aggravate effect on the IgE-mediated allergic reaction in mast cells and inflammtory;(2)Find extracellular Ca2+ has no effect on the binding of IgE and Fc?RI,but it activities GPRCA,a calcium sencing receptor,as a ligand to aggravate the currance and development of allergic reaction;(3)Further study the extracellular Ca2+-induced GPRC6A signaling pathways,and find the activiated GPRC6A causes Ca2+ influx to aggravate food allergy through the store-operated calcium entry induced by Gq signaling;(4)Also elucidate the calcium mobilization mechnisms of non-depleting CD4-blockade and glycyrrhizic acid on the food allergic reaction.In conclusion,these results indicate that extracellular Ca2÷,as a divalent cation ligand,can activate the GPRC6A expressed on the mast cell and basophils surface to aggravate the allergic reaction,and its mechanism is to promote Ca2+ influx through the store-operated calcium entry induced by Gq signaling.So the point of "extracellular Ca2+ influx is one of the main causes of the activation of allergic-related immune celus" was determined,and the regulatory of Ca2+ influx will be an important strategy to prevent and treat allergic diseases.