Urinary Leukotriene E<sub>4</sub>Concentrations Increase after Aspirin Challenge in Aspirin-sensitive Asthmatic Subjects

Christie, Pandora E.; Tagari, Philip; Ford‐Hutchinson, A. W.; Charlesson, Stella; Chee, P.; Jonathan, P.; Lee, Tak H.

doi:10.1164/ajrccm/143.5_pt_1.1025

Cited by 428 publications

(297 citation statements)

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“…In addition, urinary excretion of LTE 4 and of cotinine, the major urinary metabolite of nicotine, were also closely related. The correlation between the number of cigarettes smoked per day and the urinary excretion of LTE 4 reveals that smoking of 22 cigarettes per day results in a urinary excretion of LTE 4 that is similar to the baseline excretion of patients with asthma [15], whereas healthy volunteers [15] excreted similar amounts of LTE 4, as reported in the present study. Furthermore, smoking of more than 35 cigarettes per day enhances LTE 4 excretion to a rate that is similar to the LTE 4 excretion of asthmatics after allergen exposure.…”

Section: Discussionsupporting

confidence: 85%

Cigarette smoking stimulates cysteinyl leukotriene production in man

Fauler

Frölich

1997

Eur J Clin Investigation

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Abstract. Chronic cigarette smoking is an important risk factor for pulmonary and cardiovascular diseases. An increased production of cysteinyl leukotrienes has been shown in asthma and in cardiac ischaemia. The effect of cigarette smoking on cysteinyl leukotriene biosynthesis is, however, not known. Urinary leukotriene E 4 (LTE 4 ) was measured in 30 habitual smokers and in 30 nonsmokers. In a further 12 non-smokers urinary LTE 4 excretion was assessed before and after smoking six cigarettes. In addition, the effect of transdermal nicotine on urinary LTE 4 excretion was studied in seven nonsmokers. There was a close correlation (r ¼ 0 . 92, P < 0 . 0001) between urinary excretion of LTE 4 and the number of cigarettes smoked daily by habitual smokers. Smoking six cigarettes within 12 h resulted in a significant (P ¼ 0 . 0047), twofold increase in the mean individual LTE 4 excretion in non-smokers. Transdermal nicotine had no effect on LTE 4 excretion in non-smokers. In conclusion, cigarette smoke causes a dose-related increase in cysteinyl leukotriene production in habitual smokers. Some of the adverse effects of smoking may be related to an enhanced leukotriene synthesis.

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Section: Discussionsupporting

confidence: 85%

Cigarette smoking stimulates cysteinyl leukotriene production in man

Fauler

Frölich

1997

Eur J Clin Investigation

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“…In contrast, the urinary levels of LTE 4 remained unchanged during the course of bronchoprovocation in five asthmatics who did not develop an airway obstruction to inhaled lysineaspirin [192]. This observation was in line with concurrent reports that oral aspirin challenge increased urinary LTE 4 [214,215].…”

Section: Aspirin-induced Bronchoconstrictionsupporting

confidence: 87%

“…It has consistently been observed that the baseline urinary excretion of LTE 4 is significantly higher in aspirin-intolerant asthmatics than in aspirin-tolerant asthmatics [192,214,215]. In addition, it was recently observed that there was a marked overexpression of the LTC 4 synthase in bronchial biopsies of aspirin-intolerant asthmatics [50].…”

Section: Antileukotrienes In Aspirin-intolerant Asthmamentioning

confidence: 99%

Asthma and leukotrienes: antileukotrienes as novel anti‐asthmatic drugs

Claesson¹,

1999

Journal of Internal Medicine

101

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“…cysteinyl leukotrienes | mast cells | mucosal immunology | lung | epithelial cell C ysteinyl leukotrienes (cysLTs), leukotriene C 4 (LTC 4 ), LTD 4 , and LTE 4 are lipid mediators detected during asthma exacerbations triggered by allergen (1), aspirin (2,3), and respiratory viruses (4). The cysLTs elicit vascular permeability, inflammation, and bronchoconstriction through three G-protein-coupled receptors.…”

mentioning

confidence: 99%

Leukotriene E₄elicits respiratory epithelial cell mucin release through the G-protein–coupled receptor, GPR99

Bankova

Lai

Yoshimoto

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cysteinyl leukotrienes (cysLTs), leukotriene C 4 (LTC 4 ), LTD 4 , and LTE 4 are proinflammatory lipid mediators with pathobiologic function in asthma. LTE 4 , the stable cysLT, is a weak agonist for the type 1 and type 2 cysLT receptors (CysLTRs), which constrict airway smooth muscle, but elicits airflow obstruction and pulmonary inflammation in patients with asthma. We recently identified GPR99 as a high-affinity receptor for LTE 4 that mediates cutaneous vascular permeability. Here we demonstrate that a single intranasal exposure to extract from the respiratory pathogen Alternaria alternata elicits profound epithelial cell (EpC) mucin release and submucosal swelling in the nasal mucosa of mice that depends on cysLTs, as it is absent in mice deficient in the terminal enzyme for cysLT biosynthesis, LTC 4 synthase (LTC 4 S). These mucosal changes are associated with mast cell (MC) activation and absent in MC-deficient mice, suggesting a role for MCs in control of EpC function. Of the three CysLTRs, only GPR99-deficient mice are fully protected from EpC mucin release and swelling elicited by Alternaria or by intranasal LTE 4 . GPR99 expression is detected on lung and nasal EpCs, which release mucin to doses of LTE 4 one log lower than that required to elicit submucosal swelling. Finally, mice deficient in MCs, LTC 4 S, or GPR99 have reduced baseline numbers of goblet cells, indicating an additional function in regulating EpC homeostasis. These results demonstrate a novel role for GPR99 among CysLTRs in control of respiratory EpC function and suggest that inhibition of LTE 4 and of GPR99 may have therapeutic benefits in asthma.C ysteinyl leukotrienes (cysLTs), leukotriene C 4 (LTC 4 ), LTD 4 , and LTE 4 are lipid mediators detected during asthma exacerbations triggered by allergen (1), aspirin (2, 3), and respiratory viruses (4). The cysLTs elicit vascular permeability, inflammation, and bronchoconstriction through three G-protein-coupled receptors. The type 1 cysLT receptor (CysLTR), CysLT 1 R, is the highaffinity receptor for LTD 4 and the dominant CysLTR mediating airway smooth muscle constriction (5-8). The type 2 CysLTR, CysLT 2 R, has prominent effects on the vascular endothelium (9-12) and also elicits bronchial constriction (13,14). LTE 4 , the stable cysLT (15-18), is a weak agonist for CysLT 1 R and CysLT 2 R in transfected cells (5, 19), but elicits airflow obstruction in patients with asthma (20-22). Moreover, LTE 4 has comparable activity to LTC 4 and LTD 4 in eliciting a wheal and flare response in human skin (23), and LTE 4 elicits cutaneous vascular permeability in mice lacking both CysLT 1 R and CysLT 2 R, suggesting the existence of a high-affinity receptor for LTE 4 , which was recently identified as GPR99 (24,25). However, the mechanism by which LTE 4 induces lung pathobiology and the role of GPR99 remain poorly understood.The cysLTs are derived from arachidonate through the serial enzymatic actions of 5-lipoxygenase and leukotriene C 4 synthase (LTC 4 S). LTC 4 , the terminal product of intrac...

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Urinary Leukotriene E₄Concentrations Increase after Aspirin Challenge in Aspirin-sensitive Asthmatic Subjects

Cited by 428 publications

References 10 publications

Cigarette smoking stimulates cysteinyl leukotriene production in man

Cigarette smoking stimulates cysteinyl leukotriene production in man

Asthma and leukotrienes: antileukotrienes as novel anti‐asthmatic drugs

Leukotriene E₄elicits respiratory epithelial cell mucin release through the G-protein–coupled receptor, GPR99

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Urinary Leukotriene E4Concentrations Increase after Aspirin Challenge in Aspirin-sensitive Asthmatic Subjects

Cited by 428 publications

References 10 publications

Cigarette smoking stimulates cysteinyl leukotriene production in man

Cigarette smoking stimulates cysteinyl leukotriene production in man

Asthma and leukotrienes: antileukotrienes as novel anti‐asthmatic drugs

Leukotriene E4elicits respiratory epithelial cell mucin release through the G-protein–coupled receptor, GPR99

Contact Info

Product

Resources

About

Urinary Leukotriene E₄Concentrations Increase after Aspirin Challenge in Aspirin-sensitive Asthmatic Subjects

Leukotriene E₄elicits respiratory epithelial cell mucin release through the G-protein–coupled receptor, GPR99