Aspirin and salicylates modulate IgE-mediated leukotriene secretion in mast cells through a dihydropyridine receptor-mediated Ca²⁺ influx

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• 作者：Kana Togo ; Yoshihiro Suzuki ; Tetsuro Yoshimaru ; Toshio Inoue ; Tadashi Terui ; Toyoko Ochiai ; Chisei Ra
• 关键词：Aspirin ; Mast cells ; IgE ; Calcium ; Leukotriene ; Dihydropyridine receptor
• 刊名：Clinical Immunology
• 出版年：2009
• 出版时间：April 2009
• 年：2009
• 卷：131
• 期：1
• 页码：145-156
• 全文大小：960 K

文摘

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 LTC₄ secretion in mast cells. Therapeutic levels of aspirin and salicylates (≤ 0.3 mM, i.e., the concentrations observed in vivo in the use of antipyretic analgesic) increased IgE-mediated LTC₄ secretion. Aspirin-induced stimulation was accompanied by increased Ser-505 phosphorylation of cytosolic phospholipase A₂, which occurred independently of extracellular signal-regulated protein kinase-1/2 and p38 mitogen-activated protein kinase pathways. Aspirin also increased IgE-mediated Ca²⁺ influx, whereas aspirin at concentrations of ≥ 0.3 mM dose-dependently reduced Ca²⁺ store emptying and Ca²⁺ release-activated Ca²⁺ channel activation. Instead, aspirin facilitated a dihydropyridine receptor-mediated Ca²⁺ influx, resulting in increased LTC₄ secretion. This novel action of aspirin may play roles in exacerbation of immediate allergy and aspirin intolerance.