Lack of association between aspirin-triggered 15-hydroxyeicosatetraenoic acid release and mast cell/eosinophil activation in nasal polyps from aspirin-sensitive patients.

The mechanism of aspirin sensitivity in patients with asthma and rhinosinusitis has been attributed to arachidonic acid metabolism abnormalities.
We aimed to test whether aspirin-triggered generation of 15-hydroxyeicosatetraenoic acid (15-HETE) in nasal polyp dispersed cells (NPDCs) from aspirin-sensitive patients is associated with activation of inflammatory cells.
Polyps were obtained from 11 aspirin-sensitive and 19 aspirin-tolerant patients with chronic rhinosinusitis. NPDCs were stimulated by aspirin or calcium ionophore. Levels of 15-HETE, leukotriene (LT) C4, eosinophil cationic protein (ECP), and tryptase were measured in NPDC supernatant.
NPDCs from aspirin-sensitive patients contained more eosinophils (14% vs 9%, P < .05) and released 2.4-fold more ECP (P < .01) at baseline. Stimulation with aspirin (200 microM) resulted in a significant increase in 15-HETE generation only in tissue from aspirin-sensitive patients (mean increase, 82%) but did not induce any increase in the release of LTC4, ECP, or tryptase. Preincubation with calcium ionophore resulted in significantly enhanced generation of 15-HETE, ECP, tryptase, and LTC4 in patients from both groups. Incubation of NPDCs with misoprostol inhibited aspirin-induced 15-HETE generation in aspirin-sensitive patients and calcium ionophore-induced 15-HETE, ECP, and tryptase release in both aspirin-sensitive and aspirin-tolerant patients.
Our study demonstrated that aspirin-induced 15-HETE generation in nasal polyps from aspirin-sensitive patients is not associated with activation of mast cells and eosinophils. Misoprostol has a potent inhibitory effect on the activation of cells derived from the site of nasal mucosal inflammation, regardless of sensitivity to aspirin.
AuthorsA Lewandowska-Polak, M Jedrzejczak-Czechowicz, J S Makowska, M Jarzebska, A Jankowski, M L Kowalski
JournalJournal of investigational allergology & clinical immunology (J Investig Allergol Clin Immunol) Vol. 21 Issue 7 Pg. 507-13 ( 2011) ISSN: 1018-9068 [Print] Spain
PMID22312933 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Calcium Ionophores
  • Hydroxyeicosatetraenoic Acids
  • Misoprostol
  • 15-hydroxy-5,8,11,13-eicosatetraenoic acid
  • Arachidonate 15-Lipoxygenase
  • Aspirin
  • Adult
  • Aged
  • Aged, 80 and over
  • Arachidonate 15-Lipoxygenase (physiology)
  • Aspirin (adverse effects)
  • Calcium Ionophores (pharmacology)
  • Drug Hypersensitivity (metabolism)
  • Eosinophils (drug effects, physiology)
  • Female
  • Humans
  • Hydroxyeicosatetraenoic Acids (secretion)
  • Male
  • Mast Cells (drug effects, physiology)
  • Middle Aged
  • Misoprostol (pharmacology)
  • Nasal Polyps (immunology)

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