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Am. J. Respir. Crit. Care Med., Volume 161, Number 2, February 2000, 391-398

Differential Metabolism of Arachidonic Acid in Nasal Polyp Epithelial Cells Cultured from Aspirin-sensitive and Aspirin-tolerant Patients

MAREK L. KOWALSKI, RAFAL PAWLICZAK, JANINA WOZNIAK, KATARZYNA SIUDA, MARITA PONIATOWSKA, JOLANTA IWASZKIEWICZ, TOMASZ KORNATOWSKI, and MICHAEL A. KALINER

Department of Clinical Immunology and Allergy, and Department of Otorhinolaryngology, Medical University, Lodz, Poland; and Institute of Asthma and Allergy, Washington, DC

The mechanism of aspirin (acetylsalicylic acid [ASA]) sensitivity associated with severe asthma and chronic rhinosinusitis with nasal polyps ("aspirin triad") has been attributed to arachidonic metabolism alternations, although the putative biochemical defects have not been elucidated. The aim of this study was assessment of the hypothesis that local production of eicosanoids in the respiratory epithelium in patients with ASA-sensitive asthma/rhinosinusitis (ASARS) differs from that of ASA-tolerant patients with rhinosinusitis (ATRS). Nasal polyps were obtained from 10 patients with ASARS and 15 with ATRS during routine polypectomies, and epithelial cells (ECs) were cultured on bovine collagen type I matrix (Vitrogen 100), in medium supplemented with growth factors. The generation of eicosanoids in supernatants of confluent ECs (6 to 8 d of culture; purity > 98%) was quantified by immunoassays. Unstimulated ECs from ASARS patients generated significantly less prostaglandin E2(PGE2) compared with ATRS (0.8 ± 0.3 versus 2.4 ± 0.5 ng/µg double-stranded deoxyribonucleic acid [dsDNA], respectively), although a similar relative increase in response to calcium ionophore and inhibition with ASA was observed in both groups. Basal levels of 15-hydroxyeicosatetraenoic acid (15-HETE) were not different between groups, and calcium ionophore enhanced its production to a similar extent. However, cells incubation with 200 µM ASA for 60 min resulted in a significant increase (mean +359%) in 15-HETE generation only in ASARS patients, whereas no effect of ASA on 15-HETE generation in ATRS patients was observed. PGF2alpha generation was similar in both groups, and no significant generation of PGD2 or leukotriene C4 (LTC4) was observed in epithelial cell cultures from either group. Our results indicate that nasal polyps ECs from ASA-sensitive patients have significant abnormality in basal and ASA-induced generation of eicosanoids which may be causally related to the mechanism of ASA sensitivity. Kowalski ML, Pawliczak R, Wozniak J, Siuda K, Poniatowska M, Iwaszkiewicz J, Kornatowski T, Kaliner MA. Differential metabolism of arachidonic acid in nasal polyp epithelial cells cultured from aspirin-sensitive and aspirin-tolerant patients.




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