Aspirin and salicylates modulate IgE-mediated leukotriene secretion in mast cells through a dihydropyridine receptor-mediated Ca(2+) influx
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 seru...
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 131(2009), 1 vom: 03. Apr., Seite 145-56 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2009
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Anti-Inflammatory Agents, Non-Steroidal Calcium Channels, L-Type Salicylates Leukotriene C4 2CU6TT9V48 Immunoglobulin E 37341-29-0 Mitogen-Activated Protein Kinase 3 mehr... |
| Zusammenfassung: | 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 |
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| Beschreibung: | Date Completed 01.05.2009 Date Revised 01.12.2018 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2008.09.008 |