Mast cell CRAC channel as a novel therapeutic target in allergy

• Published in: Current opinion in allergy and clinical immunology Vol. 11; no. 1; pp. 33 - 38
• Main Authors: Di Capite, Joseph L, Bates, Grant J, Parekh, Anant B
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins, Inc 01-02-2011
• Subjects: Animals; Asthma - drug therapy; Asthma - etiology; Biophysical Phenomena; Calcium Channel Blockers - therapeutic use; Calcium Channels - drug effects; Calcium Channels - metabolism; Calcium Signaling; Feedback, Physiological; Humans; Hypersensitivity - drug therapy; Hypersensitivity - immunology; Hypersensitivity - metabolism; In Vitro Techniques; Mast Cells - drug effects; Mast Cells - immunology; Mast Cells - metabolism; Mice; Mice, Knockout; Nasal Polyps - drug therapy; Nasal Polyps - etiology
• ISSN: 1528-4050; 1473-6322
• DOI: 10.1097/ACI.0b013e32834232b0

PURPOSE OF REVIEWThis review describes recent advances in our understanding of a major Ca-entry pathway, the Ca release-activated Ca (CRAC) channel, that is central to mast cell activation.
RECENT FINDINGSAnimals in which the genes encoding the CRAC channel have been deleted have severely compromised mast cell function and reduced allergic responses. These functional consequences reflect the ability of CRAC channels to activate a range of spatially and temporally distinct responses in mast cells, which contribute to both rapid and slow phases of an allergic response. In addition, the cells can sustain their own activation through positive feedback cycles that involve CRAC channels. Drugs that inhibit CRAC channels are proving effective in treatment of allergic responses both in vitro and in animal models of asthma.
SUMMARYCRAC channels comprise a new therapeutic target for combating allergies including asthma.