Differential metabolism of arachidonic acid in nasal polyp epithelial cells cultured from aspirin-sensitive and aspirin-tolerant patients.

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 E(2)(PGE(2)) compared with ATRS (0.8 +/- 0.3 versus 2. 4 +/- 0.5 ng/microg 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 microM 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. PGF(2alpha) generation was similar in both groups, and no significant generation of PGD(2) or leukotriene C(4) (LTC(4)) 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.

[1]  E. Bardana.  Reactive airways dysfunction syndrome (RADS): fact or fantasy? , 1999, Allergy.

[2]  J. Mullol,et al.  Cyclooxygenase-2 mRNA is downexpressed in nasal polyps from aspirin-sensitive asthmatics. , 1999, American journal of respiratory and critical care medicine.

[3]  G. Melillo,et al.  Inhalation challenge in ASA-induced asthma. , 1998, Respiratory medicine.

[4]  R. Abbate,et al.  Cyclooxygenase and lipoxygenase metabolite generation in nasal polyps. , 1997, Prostaglandins, leukotrienes, and essential fatty acids.

[5]  M. Sanak,et al.  Leukotriene C 4 synthase promoter polymorphism and risk of aspirin-induced asthma , 1997, The Lancet.

[6]  A. Szczeklik.  Mechanism of aspirin‐induced asthma , 1997, Allergy.

[7]  J. Oates,et al.  Bronchial aspirin challenge causes specific eicosanoid response in aspirin-sensitive asthmatics. , 1996, American journal of respiratory and critical care medicine.

[8]  P. Bölcskei,et al.  Effect of prostaglandin E2 on eicosanoid release by human bronchial biopsy specimens from normal and inflamed mucosa. , 1996, Thorax.

[9]  M. Kowalski,et al.  Intranasal challenge with aspirin induces cell influx and activation of eosinophils and mast cells in nasal secretions of ASA‐sensitive patients , 1996, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[10]  L. Mastalerz,et al.  Protective and bronchodilator effects of prostaglandin E and salbutamol in aspirin-induced asthma. , 1996, American journal of respiratory and critical care medicine.

[11]  M. Burdick,et al.  Cultured lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis have a diminished capacity to synthesize prostaglandin E2 and to express cyclooxygenase-2. , 1995, The Journal of clinical investigation.

[12]  C. Ji,et al.  Acetylation of human prostaglandin endoperoxide synthase-2 (cyclooxygenase-2) by aspirin. , 1994, The Journal of biological chemistry.

[13]  J. Mullol,et al.  Comparison of the role of nasal polyp and normal nasal mucosal epithelial cells on in vitro eosinophil survival. Mediation by GM–CSF and inhibition by dexamethasone , 1994, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[14]  J. Oates,et al.  Eicosanoids in bronchoalveolar lavage fluid of aspirin-intolerant patients with asthma after aspirin challenge. , 1994, American journal of respiratory and critical care medicine.

[15]  S. Dahlén,et al.  The leukotriene-receptor antagonist MK-0679 blocks airway obstruction induced by inhaled lysine-aspirin in aspirin-sensitive asthmatics. , 1993, The European respiratory journal.

[16]  M. Kowalski,et al.  Nasal secretions in response to acetylsalicylic acid. , 1993, The Journal of allergy and clinical immunology.

[17]  A. Ford-hutchinson,et al.  Urinary leukotriene E4 after lysine-aspirin inhalation in asthmatic subjects. , 1992, The American review of respiratory disease.

[18]  M. Hamberg,et al.  15(S)-hydroxyeicosatetraenoic acid is the major arachidonic acid metabolite in human bronchi: association with airway epithelium. , 1990, Archives of biochemistry and biophysics.

[19]  S. Holgate,et al.  The effect of inhaled 15-(s)-hydroxyeicosatetraenoic acid (15-HETE) on airway calibre and non-specific responsiveness in normal and asthmatic human subjects. , 1990, The European respiratory journal.

[20]  S. Dahlén,et al.  Biological activities of lipoxin A include lung strip contraction and dilation of arterioles in vivo. , 1987, Acta physiologica Scandinavica.

[21]  S. Juhn,et al.  Prostaglandins, leukotrienes, and other arachidonic acid metabolites in nasal polyps and nasal mucosa , 1987, The Laryngoscope.

[22]  E. Goetzl,et al.  Abnormal responses to aspirin of leukocyte oxygenation of arachidonic acid in adults with aspirin intolerance. , 1986, The Journal of allergy and clinical immunology.

[23]  E. Goetzl,et al.  Predominant generation of 15-lipoxygenase metabolites of arachidonic acid by epithelial cells from human trachea. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[24]  E. Goetzl,et al.  IgE-dependent and ionophore-induced generation of leukotrienes by dog mastocytoma cells. , 1983, Journal of immunology.

[25]  R. Simon,et al.  Aspirin-sensitive rhinosinusitis/asthma: spectrum of adverse reactions to aspirin. , 1983, The Journal of allergy and clinical immunology.

[26]  K. Paigen,et al.  A simple, rapid, and sensitive DNA assay procedure. , 1980, Analytical biochemistry.

[27]  A. Szczeklik,et al.  Aspirin-sensitive asthma: the effect of aspirin on the release of prostaglandins from nasal polyps. , 1977, Pharmacological research communications.

[28]  A. Szczeklik,et al.  Relationship of inhibition of prostaglandin biosynthesis by analgesics to asthma attacks in aspirin-sensitive patients. , 1975, British medical journal.

[29]  M. Samter,et al.  Intolerance to aspirin. Clinical studies and consideration of its pathogenesis. , 1968, Annals of internal medicine.

[30]  M. Kowalski,et al.  Culture of human nasal epithelial cells from nasal polyps on collagen matrix. , 1998, Archivum immunologiae et therapiae experimentalis.

[31]  J Bousquet,et al.  Histochemical evidence for induction of arachidonate 15-lipoxygenase in airway disease. , 1993, The American review of respiratory disease.

[32]  J. Montserrat,et al.  Release of peptide leukotriene into nasal secretions after local instillation of aspirin in aspirin-sensitive asthmatic patients. , 1992, The American review of respiratory disease.

[33]  T. Yamashita,et al.  Etiology of nasal polyps associated with aspirin-sensitive asthma. , 1989, Rhinology. Supplement.

[34]  M. Radomski,et al.  An abnormality of arachidonic acid metabolism is not a generalized phenomenon in patients with aspirin-induced asthma. , 1988, Eicosanoids.

[35]  B. Bochner,et al.  Effect of the calcium ionophore A23187 and aspirin on histamine release in vitro from leukocytes of aspirin-intolerant donors. , 1984, International archives of allergy and applied immunology.