Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma
| Autor: | Krzysztof Sładek, F K Austen, B K Lam, Adamek L, Andrzej Szczeklik, Jerzy Soja, J F Penrose, E. Nizankowska, Stephen T. Holgate, Andrew S. Cowburn, A P Sampson |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Leukotrienes medicine.medical_specialty Biopsy T-Lymphocytes Bronchi Aspirin-induced asthma Placebos Leukocyte Count chemistry.chemical_compound Internal medicine medicine Humans Glutathione Transferase Asthma Leukotriene Aspirin Leukotriene C4 medicine.diagnostic_test biology business.industry General Medicine respiratory system medicine.disease Eosinophils Endocrinology Bronchoalveolar lavage chemistry Immunology biology.protein Cytokines Female lipids (amino acids peptides and proteins) Bronchoconstriction Cyclooxygenase medicine.symptom business Bronchoalveolar Lavage Fluid Research Article medicine.drug |
| Zdroj: | Journal of Clinical Investigation. 101:834-846 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci620 |
| Popis: | Aspirin causes bronchoconstriction in aspirin-intolerant asthma (AIA) patients by triggering cysteinyl-leukotriene (cys-LT) production, probably by removing PGE2-dependent inhibition. To investigate why aspirin does not cause bronchoconstriction in all individuals, we immunostained enzymes of the leukotriene and prostanoid pathways in bronchial biopsies from AIA patients, aspirin-tolerant asthma (ATA) patients, and normal (N) subjects. Counts of cells expressing the terminal enzyme for cys-LT synthesis, LTC4 synthase, were fivefold higher in AIA biopsies (11.5+/-2.2 cells/mm2, n = 10) than in ATA biopsies (2.2+/-0.7, n = 10; P = 0. 0006) and 18-fold higher than in N biopsies (0.6+/-0.4, n = 9; P = 0. 0002). Immunostaining for 5-lipoxygenase, its activating protein (FLAP), LTA4 hydrolase, cyclooxygenase (COX)-1, and COX-2 did not differ. Enhanced baseline cys-LT levels in bronchoalveolar lavage (BAL) fluid of AIA patients correlated uniquely with bronchial counts of LTC4 synthase+ cells (rho = 0.83, P = 0.01). Lysine-aspirin challenge released additional cys-LTs into BAL fluid in AIA patients (200+/-120 pg/ml, n = 8) but not in ATA patients (0. 7+/-5.1, n = 5; P = 0.007). Bronchial responsiveness to lysine-aspirin correlated exclusively with LTC4 synthase+ cell counts (rho = -0.63, P = 0.049, n = 10). Aspirin may remove PGE2-dependent suppression in all subjects, but only in AIA patients does increased bronchial expression of LTC4 synthase allow marked overproduction of cys-LTs leading to bronchoconstriction. |
| Databáze: | OpenAIRE |
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