Aspirin causes bronchoconstriction in aspirin-intolerant asthma (AIA) patients by triggering cysteinyl-leukotriene (cys-LT) production, probably removing PGE2-dependent inhibition. To investigate why aspirin does not cause all individuals, we immunostained enzymes of the leukotriene and prostanoid pathways bronchial biopsies from AIA patients, aspirin-tolerant (ATA) normal (N) subjects. Counts cells expressing terminal enzyme for cys-LT synthesis, LTC4 synthase, were fivefold higher...

Clinical trials with leukotriene synthesis inhibitors and cysteinyl (cys-LT) receptor antagonists have shown that cys-LTs (LTC4, LTD4, LTE4) are the predominant mediators of bronchoconstriction in response to diverse asthma triggers including allergen, PAF, sulphur dioxide, non-steroidal anti-inflammatory drugs (NSAIDs).1 In addition, inhalation a single dose cys-LT causes persistent eosinophilia bronchial mucosa sputum asthmatic patients,2 3 LT modifier significantly reduce airway blood...

Cysteinyl-leukotrienes are potent bronchoconstrictor mediators synthesized by the 5-lipoxygenase (5-LO) pathway. Eosinophilopoietic cytokines such as IL-5 enhance cysteinyl-leukotriene synthesis in eosinophils vitro, mimicking changes from asthmatic patients, but mechanism is unknown. We hypothesized that induces expression of 5-LO and/or its activating protein FLAP eosinophils, and this might be modulated anti-inflammatory corticosteroids. Compared with control cultures, increased...

Leukotrienes may mediate bronchoconstriction in asthma. Cysteinyl leukotriene production rises vivo after allergen challenge, but few reports describe concentrations clinical asthma or children. Using high performance liquid chromatography/radioimmunoassay, plasma and urinary leukotrienes asthmatic children (aged 5-10 years) were measured during an acute exacerbation (peak expiratory flow (PEF) < 65%, n = 10) one month later (PEF 74-169%, 9), non-atopic normal 1.3-13.2 years). In the...

It is postulated that a vigorous host inflammatory response in the cystic fibrosis lung contributes to injury. Tumour necrosis factor-alpha (TNF-alpha) may play part process and generation of leukotrienes. Therefore, relationships between sputum TNF-alpha, leukotriene concentration, function abnormalities 16 children with were investigated. Each subject provided samples performed spirometry. TNF-alpha was measured by enzyme linked immunosorbent assay; individual leukotrienes separated using...

Abstract In aspirin‐intolerant subjects, adverse bronchial and nasal reactions to cyclooxygenase (COX) inhibitors are associated with over‐production of cysteinyl‐leukotrienes (cys‐LTs) generated by the 5‐lipoxygenase (5‐LO) pathway. bronchi patients asthma, we previously linked cys‐LT aspirin hyper‐reactivity elevated immunoexpression in eosinophils terminal enzyme for production, LTC 4 synthase. We investigated whether this anomaly also occurs airways these patients. Immunohistochemical...

Leukotrienes derived from the 5-lipoxygenase pathway are proinflammatory lipid mediators that possibly play a role in inflammatory bowel diseases. The expression of proteins has not previously been examined colonic mucosa disease.Quantitative immunohistochemical analyses showed that, compared to those control subjects (n = 9), biopsies patients with active disease 17) had 3- 7-fold higher mean counts cells expressing (P 0.03), 5-lipoxygenase-activating protein 0.005), and leukotriene A(4)...

Rhinovirus infections cause wheeze, cough, and bronchial hyperresponsiveness. To investigate the involvement of cysteinyl-leukotrienes prostanoids in these symptoms, biopsy specimens from 9 normal subjects (nonatopic with no history chronic lung disease) were immunostained for 5-lipoxygenase (5-LO) cyclooxygenase (COX) pathway enzymes 2 weeks before 4 days after experimental infection human rhinovirus serotype 16. 5-LO-positive cell counts increased 9-fold (from 0.48 to 4.4 cells/mm(2); P...

Summary Background Human bronchial epithelial cells synthesize cyclooxygenase and 15‐lipoxygenase products, but the 5‐lipoxygenase (5‐LO) pathway that generates leukotriene (LT) family of bronchoconstrictor pro‐inflammatory mediators is thought to be restricted leucocytes. Objective We hypothesized human (HBECs) express a complete active 5‐LO for synthesis LTB 4 LTC , either constitutively or after stimulation. Methods Flow cytometry, RT‐PCR, Western blotting, enzyme immunoassays...

1. We have investigated the capacities of peripheral leukocytes from atopic asthmatic (AA) (n = 7), non-asthmatic (AN) and normal (N) 7) subjects to generate bronchoconstrictor proinflammatory mediators leukotrienes (LTs) B4 C4. 2. Mixed leukocyte preparations containing 61-84% neutrophils, 2.4-15% eosinophils, 13-29% mononuclear cells were incubated in vitro at 37 degrees C presence calcium ionophore A23187. Synthesis LTB4 LTC4 was quantitated by radioimmunoassay. 3. Both dose-response...

1. Leukotrienes (LTs) are potent pro‐inflammatory mediators with actions relevant to the pathophysiology of cystic fibrosis (CF), including increased mucus production, bronchoconstriction, leucocyte chemotaxis, and vascular permeability. We have therefore investigated potential role LTs in children CF. Leukotriene E4 levels were assessed urine 30 normal (N) (aged 1.3‐12.7 years) CF (1.6‐14.3 years). Sputum from 13 was analysed LTB4, LTC4, LTD4, LTE4. separated by reversed‐phase h.p.l.c....

Background: Excretion of leukotriene (LT) E4, the major urinary metabolite cysteinyl leukotrienes in humans, is increased patients with unstable angina and myocardial infarction, suggesting that are released into circulation during episodes ischaemia. Furthermore, known to induce potent vasoconstrictive effects human atherosclerotic coronary arteries saphenous vein. Accordingly, we measured excretion LTE4 stable artery disease both before after bypass surgery, age-matched healthy controls,...

Summary Background Nasal polyps infiltrated with eosinophils are commonly found in chronic asthmatic patients, more frequently those aspirin‐intolerant asthma (AIA) than aspirin‐tolerant (ATA). Some studies have suggested a contribution of superantigens derived from Staphylococcus sp to nasal polyposis and eosinophilia, but their relative importance AIA ATA subjects is unknown. Objective We investigated whether local production specific IgE staphylococcal enterotoxins A B (SEA SEB)...

Objectives: Leukotriene receptor antagonists (LTRA), such as montelukast, have been used a first-line treatment for patients with aspirin-intolerant asthma (AIA). This study evaluated associations between the clinical requirement LTRA and genetic polymorphisms of ALOX5, LTC4S, COX-2, CysLTR1 TBXA2R genes in arachidonic acid cascade long-term management 89 AIA from Korean population. Methods: Asthma control status was monitored 1 year maintenance medications inhaled corticosteroid oral LTRA,...

Background and Purpose The ω‐6 fatty acid‐derived lipid mediators such as prostanoids, thromboxane leukotrienes have well‐established roles in regulating both inflammation smooth muscle contractility. Resolvins are derived from ω‐3 acids important promoting the resolution of inflammation, but their activity on contractility is unknown. We investigated whether resolvin E1 (RvE1), D1 (RvD1) D2 (RvD2) can modulate contractions isolated segments rat thoracic aorta (RTA) or human pulmonary artery...

Summary Background 5‐Lipoxygenase (5‐LO) and 5‐lipoxygenase‐activating protein (FLAP) are essential for cysteinyl‐leukotriene (cys‐LT) production, critical mediators in asthma. Objective We sought to identify novel promoter polymorphisms within the FLAP (ALOX5AP) gene test role of these previously identified 5‐LO (ALOX5) Sp1 polymorphism asthma susceptibility. Methods To assess genetic association with phenotypes, we genotyped 341 Caucasian families (containing two asthmatic siblings)...

Abstract Background Fibroblasts are implicated in sub-epithelial fibrosis remodeled asthmatic airways and contribute to airway inflammation by releasing cytokines other mediators. Fibroblast activity is influenced members of the leukotriene family bronchoconstrictor inflammatory mediators, but it not known whether human bronchial fibroblasts can synthesize leukotrienes. Methods The expression biosynthetic enzymes receptors was investigated primary from bronchi normal adult subjects using...