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

Abstract

BACKGROUND:

The mechanism of aspirin sensitivity in patients with asthma and rhinosinusitis has been attributed to arachidonic acid metabolism abnormalities.

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: A Lewandowska-Polak, M Jedrzejczak-Czechowicz, J S Makowska, M Jarzebska, A Jankowski, M L Kowalski
• Journal: Journal of investigational allergology & clinical immunology (J Investig Allergol Clin Immunol) Vol. 21 Issue 7 Pg. 507-13 ( 2011) ISSN: 1018-9068 [Print] Spain
• PMID: 22312933 (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

Topics

• 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 (metabolism)
• Male
• Mast Cells (drug effects, physiology)
• Middle Aged
• Misoprostol (pharmacology)
• Nasal Polyps (immunology)