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Clin Immunol. 2009 Apr;131(1):145-56. doi: 10.1016/j.clim.2008.09.008. Epub 2009 Jan 14.

Aspirin and salicylates modulate IgE-mediated leukotriene secretion in mast cells through a dihydropyridine receptor-mediated Ca(2+) influx.

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Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Sciences, Itabashi-Ku, Tokyo, Japan.


Aspirin is a well-known nonsteroidal anti-inflammatory drug (NSAID) that may potentiate some acute allergies and causes adverse immunological reactions collectively referred to as aspirin intolerance. Aspirin intolerance is accompanied by increased leukotriene (LT) synthesis, and high levels of serum IgE are a risk factor for NSAID sensitivity. Here we demonstrate that aspirin modulates LTC(4) secretion in mast cells. Therapeutic levels of aspirin and salicylates (<or=0.3 mM, i.e., the concentrations observed in vivo in the use of antipyretic analgesic) increased IgE-mediated LTC(4) secretion. Aspirin-induced stimulation was accompanied by increased Ser-505 phosphorylation of cytosolic phospholipase A(2), which occurred independently of extracellular signal-regulated protein kinase-1/2 and p38 mitogen-activated protein kinase pathways. Aspirin also increased IgE-mediated Ca(2+) influx, whereas aspirin at concentrations of >or=0.3 mM dose-dependently reduced Ca(2+) store emptying and Ca(2+) release-activated Ca(2+) channel activation. Instead, aspirin facilitated a dihydropyridine receptor-mediated Ca(2+) influx, resulting in increased LTC(4) secretion. This novel action of aspirin may play roles in exacerbation of immediate allergy and aspirin intolerance.

[Indexed for MEDLINE]

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