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


CONCLUSIONS
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.
Department of Immunology, Rheumatology and Allergy, Chair of Clinical Immunology and Microbiology, Medical University of Łódź, Łódź, Poland. anlewa@csk.umed.lodz.pl
A
A
Lewandowska-Polak
M
M
Jedrzejczak-Czechowicz
J S
JS
Makowska
M
M
Jarzebska
A
A
Jankowski
M L
ML
Kowalski
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001093:Arachidonate 15-Lipoxygenase / Q000502:physiology; D001241:Aspirin / Q000009:adverse effects*; D061207:Calcium Ionophores / Q000494:pharmacology; D004342:Drug Hypersensitivity / Q000378:metabolism*; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D016595:Misoprostol / Q000494:pharmacology; D009298:Nasal Polyps / Q000276:immunology*
D061207:Calcium Ionophores; D006893:Hydroxyeicosatetraenoic Acids; D016595:Misoprostol; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001093:Arachidonate 15-Lipoxygenase; D001241:Aspirin