Mast Cell Mediators in Allergic Inflammation and Mastocytosis

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Histamine

Histamine is an amine produced by the decarboxylation of histidine, and it is stored in the secretory granules of all mature mast cells including connective tissues, mucosal membranes, skin and basophils [50], [51]. No differences are seen in the amounts of histamine stored in mast cells reflecting a similar mechanism for synthesis and storage [50], [51]. Once released into circulation, histamine is metabolized by histamine methyl transferase after one pass through the system. Plasma histamine

Membrane-derived lipid mediators

Human mast cells generate and release eicosanoid lipid mediators through a transmembrane activation signal with calcium influx [45], [90]. Prostaglandins and leukotrienes are metabolic products of AA derived from membrane phospholipids through the action of phospholipase enzymes (eg, PLA2) [91]. Other products of AA include hydroxyeicosatetraenoic acids (HETEs), lipoxins, epoxyeicosatrienoic acids, and isopropanes, which contribute to modulate inflammatory responses [92]. Cytosolic (type IV)

Chemokines and cytokines

Human mast cells are a source of multifunctional cytokines, but little is known of the regulation and secretion of cytokines and chemokines by patients with mastocytosis. [129]. Preformed TNFα, found in human skin and pulmonary mast cell granules, is released after IgE-, IgG-, and TLR-mediated activation. High-density oligonucleotide probe arrays (GeneChip analysis) have permitted elucidation of the cytokine gene expression pattern after mast cells have been activated through FcɛRI ligation and

Summary

Mast cells possess an array of potent inflammatory mediators capable of inducing acute symptoms after cell activation, including urticaria, angioedema, bronchoconstriction, diarrhea, vomiting, hypotension, cardiovascular collapse, and death in few minutes. In contrast, mast cells can provide an array of beneficial mediators in the setting of acute infections, cardiovascular diseases, and cancer. The balance between the detrimental and beneficial roles of mast cells is not completely understood.

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