Leukotrienes mediate part of Ova-induced lung effects in mice via EGFR

2003 ◽  
Vol 285 (4) ◽  
pp. L808-L818 ◽  
Author(s):  
B. Boris Vargaftig ◽  
Monique Singer
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Egf Receptor ◽  
Kinase Inhibitor ◽  
Airway Remodeling ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Egfr Tyrosine Kinase Inhibitor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Cysteinyl Leukotriene

Antigen induces murine bronchial hyperreactivity (BHR), inflammation, mucus accumulation, and airway remodeling. To investigate whether leukotrienes (LT) mediate the effects of antigen [ovalbumin (Ova)], we studied 5-lipoxygenase (5-LO) expression in immunized BP2 mice and blocked LT synthesis with the 5-LO inhibitor zileuton or antagonized their effects with receptor antagonists [cysteinyl leukotriene (Cys-LT)-ra MK-571, LY-171883; LTB4-ra PH-163]. Cys-LT content increased in the bronchoalveolar lavage fluid (BALF) as early as 15 min after the intratracheal instillation of Ova. Zileuton inhibited LT release in the BALF and eosinophil recruitment in the lungs, and dose dependently reduced BHR, mucus accumulation, and remodeling, as did the LT-ra. Thus LT, released just after antigen challenge, might constitute the first step in accounting for the effects of Ova. Because mucus accumulation is regulated via the EGF receptor (EGFR), which is also implicated in the effects of LT, we studied this pathway with AG-1478, an EGFR tyrosine kinase inhibitor given at 0.5, 4, and 20 mg/kg. AG-1478 inhibited BHR, inflammation, and lung remodeling induced by Ova or by molecules themselves generated by Ova, such as LT, IL-13, and monocyte chemoattractant protein-1, which promote identical effects, suggesting the involvement of the EGFR pathway in the asthma-like syndrome observed.

scholarly journals Protective Effects of Nintedanib against Polyhexamethylene Guanidine Phosphate-Induced Lung Fibrosis in Mice

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1974 ◽  
Author(s):  
Hyeon-Young Kim ◽  
Min-Seok Kim ◽  
Sung-Hwan Kim ◽  
Doin Joen ◽  
Kyuhong Lee
Keyword(s):  
Lung Fibrosis ◽  
Bronchoalveolar Lavage Fluid ◽  
Kinase Inhibitor ◽  
Pulmonary Inflammation ◽  
Intratracheal Instillation ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Protective Effects ◽  
Polyhexamethylene Guanidine ◽  
Guanidine Phosphate

Nintedanib (NDN), a tyrosine kinase inhibitor, has been shown to have anti-tumor, anti-inflammatory, and anti-fibrotic effects in several reports. We investigated the protective effects of NDN against polyhexamethylene guanidine phosphate (PHMG)-induced lung fibrosis in mice. The following three experimental groups were evaluated: (1) vehicle control; (2) PHMG (1.1 mg/kg); and (3) PHMG & NDN (60 mg/kg). PHMG induced pulmonary inflammation and fibrosis by intratracheal instillation in mice. In contrast, NDN treatment effectively alleviated the PHMG induced lung injury, and attenuated the number of total cells and inflammatory cells in the bronchoalveolar lavage fluid, including the fibrotic histopathological changes, and also reduced the hydroxyproline content. NDN also significantly decreased the expression of inflammatory cytokines and fibrotic factors, and the activation of the NLRP3 inflammasome in lung tissues. These results suggest that NDN may mitigate the inflammatory response and development of pulmonary fibrosis in the lungs of mice treated with PHMG.

Antimacrophage chemokine treatment prevents neutrophil and macrophage influx in hyperoxia-exposed newborn rat lung

2004 ◽  
Vol 286 (3) ◽  
pp. L488-L493 ◽  
Author(s):  
Michael A. Vozzelli ◽  
S. Nicholas Mason ◽  
Mary H. Whorton ◽  
Richard L. Auten
Keyword(s):  
Inflammatory Response ◽  
Bronchoalveolar Lavage ◽  
Protein Oxidation ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Lung Cells ◽  
Newborn Rats ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Cellular Inflammatory Response

Macrophage-derived cytokines may provoke the inflammatory response in lung injury. Because macrophage influx is a prominent feature of the cellular inflammatory response accompanying the development of bronchopulmonary dysplasia, we hypothesized that blocking macrophage influx would reduce overall cellular influx and oxidative damage. Newborn rats were exposed at birth to 95% O2or air for 1 wk, and hyperoxia-exposed pups were injected with anti-monocyte chemoattractant protein-1 (MCP-1) or IgG control on days 3–5. MCP-1 was increased in bronchoalveolar lavage fluid and in histological sections from the 95% O2-exposed, IgG-injected pups compared with air-exposed controls. At 1 wk, anti-MCP-1-treated pups had reduced leukocyte numbers, both macrophages and neutrophils, in bronchoalveolar lavage fluid compared with IgG-treated controls. Cytokine-induced neutrophil chemoattractant-1, the rat analog of IL-8, was not significantly decreased in lavage fluid but was reduced in lung cells in anti-MCP-1-treated pups. Tissue carbonyls, a measure of protein oxidation, were decreased in anti-MCP-1-treated pups. Anti-MCP-1 treatment prevented neutrophil influx and reduced protein oxidation in hyperoxia-exposed newborn rats.

scholarly journals Sex differences in the induction of angiotensin converting enzyme 2 (ACE-2) in mouse lungs after e-cigarette vapor exposure and its relevance to COVID-19

2021 ◽  
pp. jim-2020-001768
Author(s):  
Vegi Naidu ◽  
Amir A Zeki ◽  
Pawan Sharma
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Mouse Lung ◽  
Dependent Manner ◽  
Monocyte Chemoattractant Protein 1 ◽  
Angiotensin Converting Enzyme 2 ◽  
Female Mice ◽  
Monocyte Chemoattractant ◽  
Impaired Lung Function ◽  
Mouse Lungs

The COVID-19 pandemic has affected over 114 million people and has resulted in >2.5 million deaths so far. Some people have greater susceptibility which influences both SARS-CoV-2 infectivity and COVID-19 severity. Smoking is associated with increased ACE-2, the receptor for SARS-CoV-2, which facilitates its entry through the lung. However, despite the widespread use of e-cigarettes, also known as ‘vaping’, little is known regarding the effects of vaping on ACE-2 expression and how this affects SARS-CoV-2 infection. In addition, the added effect of nicotine in the vapor is also unknown. Thus, we tested whether vaping induces ACE-2 expression in the mouse lung. BALB/c mice exposed to e-cigarette vapor (±nicotine) resulted in a significant increase in peribronchiolar inflammation and influx of immune cells into the airways. Vapor increased monocyte chemoattractant protein-1, interleukin 1β, and KC levels in bronchoalveolar lavage fluid in both sexes, which were further enhanced by nicotine (whereas increase in interleukin 6 was sex and nicotine independent). The reduction in basal inspiratory capacity with vapor exposure occurred independent of sex or nicotine. The increase in methacholine-induced airway hyper-responsiveness was independent of sex; however, in female mice it was only significant in the nicotine-exposed group. Lung ACE-2 expression was increased in male mice in a nicotine-dependent manner as compared with female mice. Collectively, while vaping (±nicotine) induced airway inflammation and impaired lung function, the induction of lung ACE-2 occurred to a significantly greater degree in males exposed to vapor containing nicotine as compared with females. Thus, via these effects on ACE-2 expression in the lungs and airways, vaping itself may facilitate SARS-CoV-2 entry into the airways.

CYSTEINYL LEUKOTRIENE LEVELS IN BRONCHOALVEOLAR LAVAGE FLUID OF PEDIATRIC LUNG TRANSPLANT RECIPIENTS

CHEST Journal ◽  
2007 ◽  
Vol 132 (4) ◽  
pp. 606B
Author(s):  
Binal S. Kancherla ◽  
Marc Schecter ◽  
Haibin Zhang ◽  
John Robertson ◽  
Minh Doan ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Lung Transplant ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Transplant Recipients ◽  
Cysteinyl Leukotriene ◽  
Lung Transplant Recipients

scholarly journals S1PR2 Inhibition Attenuates Allergic Asthma Possibly by Regulating Autophagy

2021 ◽  
Vol 11 ◽  
Author(s):  
Hanye Liu ◽  
Liangchang Li ◽  
Zhengai Chen ◽  
Yilan Song ◽  
Weidong Liu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Expression ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Cell ◽  
Airway Remodeling ◽  
Lavage Fluid ◽  
Expression Levels ◽  
Sphingosine 1 Phosphate ◽  
Masson Staining

This study is to investigate the role of Sphingosine-1-phosphate (S1P) in the asthma progression, and the involvement of autophagy. Airway remodeling mice were subjected to the HE, PAS, and Masson staining. Protein expression levels in the tissues, samples and model cells were detected with ELISA, Western blot analysis, and immunohistochemical/immunofluorescent analysis. The S1P2 receptor antagonist JTE-013 decreased the inflammatory cell infiltration and goblet cell production in asthmatic mice tissues. The IL-1, IL-4, IL-5 and serum IgE contents were decreased in bronchoalveolar lavage fluid, while the Beclin1 expression in lung tissues was decreased. The LC3B1 to LC-3B2 conversion was decreased, with increased P62 accumulation and decreased p-P62 expression. In airway remodeling mice, JTE-013 significantly decreased collagen deposition in lung tissues and decreased smooth muscle cell smooth muscle activating protein expression. In lung tissue, the expression levels of Beclin1 were decreased, with decreased LC3B1 to LC-3B2 conversion, as well as the increased P62 accumulation and decreased p-P62 expression. However, these effects were reversed by the RAC1 inhibitor EHT 1864. Similar results were observed for the silencing of S1P2 receptor in the cells, as shown by the decreased Beclin1 expression, decreased LC3B1 to LC-3B2 conversion, increased P62 accumulation, and decreased p-P62 expression. The smooth muscle activators were significantly decreased in the JTE-013 and EHT1864 groups, and the EHT 1864 + S1P2-SiRNA expression level was increased. S1P is involved in the progression of asthma and airway remodeling, which may be related to the activation of S1PR2 receptor and inhibition of autophagy through RAC1.

scholarly journals Cysteinyl Leukotrienes Impair Hypoxic Pulmonary Vasoconstriction in Endotoxemic Mice

2011 ◽  
Vol 115 (4) ◽  
pp. 804-811 ◽  
Author(s):  
Bodil Petersen ◽  
K. Frank Austen ◽  
Kenneth D. Bloch ◽  
Yukako Hotta ◽  
Fumito Ichinose ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Lavage Fluid ◽  
Wild Type ◽  
Cysteinyl Leukotrienes ◽  
Endotoxin Challenge ◽  
Cysteinyl Leukotriene ◽  
Leukotriene Receptor ◽  
Cysteinyl Leukotriene Receptor

Background Sepsis impairs hypoxic pulmonary vasoconstriction (HPV) in patients and animal models, contributing to systemic hypoxemia. Concentrations of cysteinyl leukotrienes are increased in the bronchoalveolar lavage fluid of patients with sepsis, but the contribution of cysteinyl leukotrienes to the impairment of HPV is unknown. Methods Wild-type mice, mice deficient in leukotriene C(4) synthase, the enzyme responsible for cysteinyl leukotriene synthesis, and mice deficient in cysteinyl leukotriene receptor 1 were studied 18 h after challenge with either saline or endotoxin. HPV was measured by the increase in left pulmonary vascular resistance induced by left mainstem bronchus occlusion. Concentrations of cysteinyl leukotrienes were determined in the bronchoalveolar lavage fluid. Results In the bronchoalveolar lavage fluid of all three strains, cysteinyl leukotrienes were not detectable after saline challenge; whereas endotoxin challenge increased cysteinyl leukotriene concentrations in wild-type mice and mice deficient in cysteinyl leukotriene receptor 1, but not in mice deficient in leukotriene C(4) synthase. HPV did not differ among the three mouse strains after saline challenge (120 ± 26, 114 ± 16, and 115 ± 24%, respectively; mean ± SD). Endotoxin challenge markedly impaired HPV in wild-type mice (41 ± 20%) but only marginally in mice deficient in leukotriene C(4) synthase (96 ± 16%, P < 0.05 vs. wild-type mice), thereby preserving systemic oxygenation. Although endotoxin modestly decreased HPV in mice deficient in cysteinyl leukotriene receptor 1 (80 ± 29%, P < 0.05 vs. saline challenge), the magnitude of impairment was markedly less than in endotoxin-challenged wild-type mice. Conclusion Cysteinyl leukotrienes importantly contribute to endotoxin-induced impairment of HPV in part via a cysteinyl leukotriene receptor 1-dependent mechanism.

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