Faculty Opinions recommendation of Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytes.

2014 ◽  
Author(s):  
Alkis Psaltis ◽  
Ahmed Bassiouni
Keyword(s):  
Respiratory Disease ◽  
Cysteinyl Leukotriene ◽  
Aspirin Exacerbated Respiratory Disease ◽  
Adherent Leukocytes

scholarly journals Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytes

Blood ◽  
2012 ◽  
Vol 119 (16) ◽  
pp. 3790-3798 ◽  
Author(s):  
Tanya M. Laidlaw ◽  
Molly S. Kidder ◽  
Neil Bhattacharyya ◽  
Wei Xing ◽  
Shiliang Shen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Respiratory Disease ◽  
Peripheral Blood ◽  
Nasal Polyps ◽  
Tissue Inflammation ◽  
Cysteinyl Leukotriene ◽  
Aspirin Exacerbated Respiratory Disease ◽  
Platelet Adherence ◽  
Adherent Leukocytes ◽  
Respiratory Tissue

Abstract Cysteinyl leukotriene (cysLT) overproduction is a hallmark of aspirin-exacerbated respiratory disease (AERD), but its mechanism is poorly understood. Because adherent platelets can convert the leukocyte-derived precursor leukotriene (LT)A4 to LTC4, the parent cysLT, through the terminal enzyme LTC4 synthase, we investigated the contribution of platelet-dependent transcellular cysLT production in AERD. Nasal polyps from subjects with AERD contained many extravascular platelets that colocalized with leukocytes, and the percentages of circulating neutrophils, eosinophils, and monocytes with adherent platelets were markedly higher in the blood of subjects with AERD than in aspirin-tolerant controls. Platelet-adherent subsets of leukocytes had higher expression of several adhesion markers than did platelet nonadherent subsets. Adherent platelets contributed more than half of the total LTC4 synthase activity of peripheral blood granulocytes, and they accounted for the higher level of LTC4 generation by activated granulocytes from subjects with AERD compared with aspirin-tolerant controls. Urinary LTE4 levels, a measure of systemic cysLT production, correlated strongly with percentages of circulating platelet-adherent granulocytes. Because platelet adherence to leukocytes allows for both firm adhesion to endothelial cells and augmented transcellular conversion of leukotrienes, a disturbance in platelet-leukocyte interactions may be partly responsible for the respiratory tissue inflammation and the overproduction of cysLTs that characterize AERD.

scholarly journals Effect of TGF-β1 on eosinophils to induce cysteinyl leukotriene E4 production in aspirin-exacerbated respiratory disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256237
Author(s):  
Youngwoo Choi ◽  
Soyoon Sim ◽  
Dong-Hyun Lee ◽  
Hee-Ra Lee ◽  
Ga-Young Ban ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Cysteinyl Leukotriene ◽  
Aspirin Exacerbated Respiratory Disease ◽  
Healthy Control ◽  
Tgf Β1 ◽  
Eosinophil Degranulation

Cysteinyl leukotriene (cysLT) overproduction and eosinophil activation are hallmarks of aspirin-exacerbated respiratory disease (AERD). However, pathogenic mechanisms of AERD remain to be clarified. Here, we aimed to find the significance of transforming growth factor beta 1 (TGF-β1) in association with cysteinyl leukotriene E4 (LTE4) production, leading to eosinophil degranulation. To evaluate levels of serum TGF-β1, first cohort enrolled AERD (n = 336), ATA (n = 442) patients and healthy control subjects (HCs, n = 253). In addition, second cohort recruited AERD (n = 34) and ATA (n = 25) patients to investigate a relation between levels of serum TGF-β1 and urinary LTE4. The function of TGF-β1 in LTE4 production was further demonstrated by ex vivo (human peripheral eosinophils) or in vivo (BALB/c mice) experiment. As a result, the levels of serum TGF-β1 were significantly higher in AERD patients than in ATA patients or HCs (P = .001; respectively). Moreover, levels of serum TGF-β1 and urinary LTE4 had a positive correlation (r = 0.273, P = .037). In the presence of TGF-β1, leukotriene C4 synthase (LTC4S) expression was enhanced in peripheral eosinophils to produce LTE4, which sequentially induced eosinophil degranulation via the p38 pathway. When mice were treated with TGF-β1, significantly induced eosinophilia with increased LTE4 production in the lung tissues were noted. These findings suggest that higher levels of TGF-β1 in AERD patients may contribute to LTE4 production via enhancing LTC4S expression which induces eosinophil degranulation, accelerating airway inflammation.

scholarly journals Omalizumab reduces cysteinyl leukotriene and 9α,11β-prostaglandin F2 overproduction in aspirin-exacerbated respiratory disease

2016 ◽  
Vol 137 (5) ◽  
pp. 1585-1587.e4 ◽  
Author(s):  
Hiroaki Hayashi ◽  
Chihiro Mitsui ◽  
Eiji Nakatani ◽  
Yuma Fukutomi ◽  
Keiichi Kajiwara ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Cysteinyl Leukotriene ◽  
Aspirin Exacerbated Respiratory Disease

Bedeutung der allergologischen Abklärung bei Asthma und COPD

2014 ◽  
Vol 71 (5) ◽  
pp. 267-274
Author(s):  
Judith A. Schneider Spence ◽  
Andreas J. Bircher ◽  
Kathrin Scherer Hofmeier
Keyword(s):  
Respiratory Disease ◽  
Asthma Bronchiale ◽  
Aspirin Exacerbated Respiratory Disease ◽  
Work Up

Während eine allergologische Abklärung im Work-Up eines Asthma bronchiale inbegriffen sein sollte, wird die chronisch obstruktive Pneumopathie nicht spontan mit einer atopischen Diathese in Zusammenhang gebracht. Anamnese, Klinik, das Vorhandensein weiterer atopischer Krankheiten sowie Prickteste und die serologische Messung von spezifischen IgE-Antikörpern geben Hinweise auf eine allergische Genese einer akuten oder chronischen Lungenkrankheit. Der Stickoxidwert in der Ausatemluft (FeNO-Messung) kann durch die Infiltration von Eosinophilen in die Bronchialwand beim allergischen Phänotyp des Asthma bronchiale erhöht sein (TH2-gewichteter Phänotyp). Eine Abhängigkeit der Beschwerden vom Arbeitsplatz muss evaluiert werden. Neben dem allergischen Typ des Asthma bronchiale soll auch an eine Aspirin-exacerbated-respiratory disease (AERD) gedacht werden. Aufgrund der überlappenden pathophysiologischen Grundlagen und der Symptomatik zwischen Asthma bronchiale und der chronisch obstruktiven Pneumopathie ist die Zuweisung zum Allergologen allenfalls auch bei einem COPD-Patienten indiziert.

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