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

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2009-04, Vol.131 (1), p.145-156
• Main Authors: Togo, K, Suzuki, Y, Yoshimaru, T, Inoue, T, Terui, T, Ochiai, T, Ra, C
• Format: Article
• Language: English
• ISSN: 1521-6616
• DOI: 10.1016/j.clim.2008.09.008

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 sub(4) secretion in mast cells. Therapeutic levels of aspirin and salicylates ( approximately equal to 0.3 mM, i.e., the concentrations observed in vivo in the use of antipyretic analgesic) increased IgE-mediated LTC sub(4) secretion. Aspirin-induced stimulation was accompanied by increased Ser-505 phosphorylation of cytosolic phospholipase A sub(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 super(2) super(+) influx, whereas aspirin at concentrations of >=0.3 mM dose-dependently reduced Ca super(2) super(+) store emptying and Ca super(2) super(+) release-activated Ca super(2) super(+) channel activation. Instead, aspirin facilitated a dihydropyridine receptor-mediated Ca super(2) super(+) influx, resulting in increased LTC sub(4) secretion. This novel action of aspirin may play roles in exacerbation of immediate allergy and aspirin intolerance.